...Welcome back, everyone, to the 2024 RBC Global Healthcare Conference. My name is Greg Renza, the Senior Biotechnology Equity Research Analyst here at RBC, and we're pleased to have Nurix Therapeutics today. Joining us from the company is Arthur Sands, the President and CEO. Of course, if you have any questions for Arthur in the audience, do please feel free to ask those during our Q&A at the end. With that, Arthur, it's great to see you. Thanks for having us, Greg. It's great to be here. I think we'll just have you kick it off just with an intro for those who aren't as familiar with Nurix, and a brief introduction to the company. Sure. So, before I lead into that, just, I will be making certain forward-looking statements and refer you to our risk factors filed with the SEC. We're advancing a very broad pipeline, which I'm showing on this slide for those of you who can see the slides. We've been focused with our wholly owned pipeline on BTK degraders. These are molecules, NX-5948 and NX-2127, that degrade BTK, which of course a highly validated target in B-cell malignancies. And 5948 is advancing primarily in CLL, while 2127 is more focused as a dual degrader mechanism, not only BTK, but IMiD-like activity, so Revlimid-like activity, combined with a BTK degrader. So we're focused there on aggressive lymphomas, such as diffuse large B-cell lymphoma, and mantle cell lymphoma. We also have NX-1607, which is a Cbl-B inhibitor. This is an inhibitor of an E3 ligase, which raises protein levels. The degraders will suppress protein levels, and this is an immuno-oncology being developed in phase 1 across approximately 11 different solid tumor indications currently. We have multiple programs with partners, Sanofi, Gilead, and Pfizer, formerly Seagen, focused on using our targeted protein degraders in hitched to antibodies as a new form of ADCs, which we call degrader antibody conjugates. So very broad pipeline in oncology, as well as now moving into inflammation and immunology with several programs, most notably the IRAK4 degrader, which was licensed by Gilead. And also, we recently announced a STAT6 program, a degrader of STAT6, with Sanofi. And for all of our partnerships, we maintain cost profit share options, after initial human development. So that's just a quick pipeline overview. That, that's great, and certainly, I think, the maturity and the updates on the I I aspect of the Nurix story have been rather interesting and robust over the last several time periods. But maybe we'll stick with certainly with the B-cell side, with 2127 and 5948. Just to build a little bit, Arthur, on the what's being explored here. You mentioned the BTK with 5948, but also the duality of 2127. How do we think about these two programs in a comparative way? Yeah, let me skip over to what's labeled as slide 64, so the slide numbers don't actually make sense. But this is a slide that shows how we see 5948 fitting with 2127 across the B-cell malignancy landscape. So the landscape of B-cell malignancies pictured here, the circles represent the relative size of each indication in terms of patient numbers. CLL or chronic lymphocytic leukemia is one of the most common, is the most common adult leukemia. 5948, we see really with the potential to be addressing this whole area of CLL, as well as Waldenstrom's and other indolent leukemia lymphomas, which are pictured to the left side here. And that's because as a pure BTK degrader, 5948 can address these. The BTK mechanism works. We know this through the success of BTK inhibitors. We have superior aspects to a degrader, which I'm sure we'll talk about a little bit later, Greg. And then if you look at 2127 across the bottom there, we see that really predominantly in the DLBCL, which is diffuse large B-cell, and MCL categories in terms of these aggressive lymphomas. And here, a dual acting agent or a combination agent, which is essentially what 2127 is, combining BTK plus IMiD-like activity, is really required to get dramatic responses. And we've actually seen some dramatic complete responses in each of these categories. So that's how we see really providing the first-in-class and best-in-class degraders to address multiple aspects of B-cell malignancies. Right. So certainly a complex market, but many slices to the pie and two assets that can speak to that. But we know that NX-5948, you'll be sharing an efficacy update at mid-2024. Just provide us, Arthur, with a preview of what we should be looking for in terms of focus, patient numbers, maybe the extent of those efficacy readouts as you build on this program. Yeah. So we are focused on NX-5948 for a mid-year update. We will be at EHA. This is the trial design I'm showing now on the slide labeled 65, NX-5948 trial design. This is the trial status at our last presentation at ASH. So at EHA, it'll be another full six months more of enrollment and data compared to the ASH. You can see at this time, the arrows indicating where we were in dose escalation for CLL and NHL. They had their separate dose escalation for NX-5948. So we should pretty well cover all of the doses essentially for the EHA update. As I mentioned, six months more of data, a significant number, a greater number of patients, as well as length of follow-up for each patient, duration of therapy for each patient. Then we are enrolling patients in every category, as we mentioned earlier, to the right. But at the EHA update for this, we're really going to be focusing on CLL rather than the NHL categories. And the goal here will be to look at the doses across the board in CLL and see if we can identify doses that we think would be the doses to select for expansion. So, greater number of patients, longer duration of follow-up at EHA. And then also, very importantly, further description of the resistance mutation story and how our degrader can address these resistance mutations, which is a big part of the scientific advantage of degraders. Okay, all right. And then what would be a reasonable benchmark, maybe to evaluate this data? You know, folks, to us, bring up BeiGene's 16673, the 70% ORR at ASH last year. And I know comparisons are difficult, but there are some reference points that folks are looking at as you're thinking about, you know, more of these patients and the dose levels. Yeah. So, what we've guided to is between 50%-70% ORR across all of our dose levels. So we're ranging from 50 milligrams to 600 here in CLL. So that's quite a dose range, and therefore, we bracket what our, you know, target ORR is between 50%-70%. Clearly, at an optimized dose or at higher doses, 70% would be, you know, interesting success target. But that's what we've guided. It is hard to compare between trials. We are also enrolling... If you look at the slide, the bottom, the CNS patients with CNS involvement, both primary CNS lymphoma and secondary CNS lymphoma, as well as CLL with CNS involvement. So I mention that because that's a very challenging category of patient. I don't believe others are enrolling in that category, so we do have a very advanced patient population and also one with a large number of resistance mutations. So- Yeah. But we will be providing that update. Maybe just building on what you mentioned, Arthur, just on the blood-brain barrier, certainly indicated from the AACR data with those patients who have CNS involvement. How significant is that, just to build on what you're pointing to? Well, so in general, across all of the CNS lymphoma leukemias, you're looking at 5% or so of patients, and very severe disease category. In general, there's no real therapy for these patients. We have reported on our first complete response, seeing with a primary CNS lymphoma patient, and then also a partial response, quite significant partial response in a CLL patient, and that was the AACR presentation with CNS involvement, who actually had complete clearance of the tumor cells from the cerebrospinal fluid, which was quite a result, and long duration of the therapy. So we think this is going to be a potential distinguishing feature for NX-5948. We showed that it does cross the blood-brain barrier. We see the drug in the CSF, we see this clear clinical activity. Sometimes we get the question, "Well, it's only 5% of patients." Well, 5% of patients in high unmet medical need. Mm-hmm. But I also think it's important, if we look at the CLL case, for example, that patient had been on acalabrutinib, when they developed CNS disease. So, the way I look at it, too, is if you could take a degrader like 5948, and keep the disease out of the CNS, then you're looking at 95% of patients who would really prefer not to get CNS disease in the first place. So I think that's going to be a potential distinguishing feature, when we're just talking about CNS activity. That makes sense. And then as we see here, the 1B dose expansion, maybe just thinking more forward-looking, just help us outline a potential path towards registration for 5948, possible accelerated approval options, what those timelines could look like. So we do have fast track status for 5948 already, which has been focused on the post-BTK inhibitor, post-BCL-2 inhibitor line of therapy, so third line plus line of therapy. So that is clearly an area of high unmet medical need and one that could be eligible for accelerated approval. But we think there's more, there's more opportunity than that, actually, because we think 5948 could move up in lines of therapy. So based on the profile we're seeing against these resistance mutations, et cetera, we think that a second-line confirmatory trial would also make sense. We haven't outlined these plans yet, specifically. That'll be, I think, a second half... sort of idea based on the data, the totality of the data. But then we're also very interested in some small potential rapid indications, such as Waldenstrom's, which is an NHL that is high on that medical need, could also be accelerated approval type of pathway. And then, of course, we talked about the CNS lymphoma. So there's we look at, you know, multiple approaches. We haven't outlined exactly what the pivotal approach. It'll likely be more than one pivotal trial- Yeah. so that we can cover some of the smaller, faster indications, as well as this larger, what will be a slower, you know, approval pathway in CLL, for example. So a combination of these kinds of pivotal trials. All right. That's great. You nicely laid out 5948 positioning with 2127, and I'm sure we'll come back to 5948. But just in going with 2127, just the BTK degradation, the IMiD activity, are there synergistic effects that we can anticipate from this dual approach for 2127? Well, definitely. So part of the theory of the combination for 2127, I think we're gonna be talking about, again, DLBCL, for example. There have been some trials done with combining ibrutinib with lenalidomide and rituximab, and those three, in combination, have produced some pretty dramatic results with DLBCL. And similar to what we're seeing with 2127, which combines BTK degradation with IMiD-like activity. And I'm referring to trials done at MD Anderson with that triple combination set. So, now, with 2127, it's a single agent, oral, once a day, so very convenient. We're enrolling patients that have been post-CAR T, post-bispecific failures, as an oral agent. And we've seen, as I mentioned, some impressive complete responses, as case studies so far. The one patient I'm recalling, an 84-year-old woman, had been on R-CHOP, R-ICE, and was actually CAR T ineligible, had been on rituximab, ibrutinib, and lenalidomide, and then came onto our trial, and she had a complete response within the 8 weeks and has now gone over 18 months of duration of response. So we see the duality, the combination effect really being important, and 2127 puts it in one molecule. Yeah. And then maybe just the plans to start the 1B expansion portion of 2127 in DLBCL, MCL, as well as CLL. This is following the recent lift of the clinical hold. Yeah. So we had the partial clinical hold lifted for 2127, so we're focused on MCL now, and DLBCL, with the new chirally controlled product, which actually will be, we believe, the commercial form of the product. So we've got through an important next step in the production of that. It is produced, and we're ready to restart that clinical trial, and those two indications will be the primary emphasis. Yeah. And as you mentioned, manufacturing versus anything else, which was the result and the impetus behind the hold, and that has been resolved, which sets you up for the next stage. That has, that has been completely resolved. Mm-hmm. And that is the product has. We've manufactured it. It's Yeah ... being distributed to sites, and protocols cleared the FDA, et cetera. And important to note that 5948 does not have that manufacturing issue. Right. It's a totally separate molecule. Great. Great. And I think you lay it out nicely in this slide, and you speak to it nicely, but, you know, we always get the questions about how are you prioritizing between the two assets? I think the markets speak for themselves, but I just want to give you an opportunity to kind of opine on that broader landscape and basically the prioritization between 5948 and 2127 for Nurix. The two compounds are truly differentiated. Yeah. They're very, very different compounds. And, so they actually have prioritized themselves- Exactly ... in their own way. NX-5948 has been accelerating. It did not have the manufacturing- Mm-hmm ... issue to overcome, and enrollment has been accelerating in 5948, so it really is a priority. I also do want to talk to the mutational, resistance mutation story, which 5948 addresses here on this slide, where it's. I'm showing the heat map. The different colors indicate where the BTK inhibitors have failed, and the mutations are across the top, the C481S, the B416, and T474, and 528W. Those are the most common mutations we're seeing in the clinic. And 5948 really can address all of them. So you see we're very potent across the board, there, whereas all the inhibitors have different liabilities with these resistance mutations. So this really sets the stage for 5948's potential superiority to all BTK inhibitors, which is an $8 billion market. And again, being a once-a-day oral drug, with a very well-tolerated safety profile, puts it in a category to be prioritized very highly, I would say. Your question- Yeah ... was about prioritization. Yeah. This is a very, very, large potential future, drug agent here, and so moving it forward as quickly as possible, to address these emerging resistance mutations, I think is critical. That's great. Any questions from the audience on the oncology side before we shift to I&I?... Great. Let's keep moving. So, Arthur, as you've mentioned in your opener, multiple recent announcements, just highlighting that growing role of inflammation and immunology programs at I&I in the pipeline. So why is targeted protein degradation maybe advantageous for I&I development? So, you know, I can address that with by talking about a little bit more about the BTK case story with targeted protein degradation on the slide. That is a cartoon of comparing inhibitors, which are in the center panel, that purple dot that's blocking BTK, blocks really just one arm of the signaling pathway. And that is overcome by degradation all the way to the right. We take out the scaffolding function as well as the kinase function, so the big, you know, two X's versus where only one block. And this is important because the totality of the signal is very strong through the scaffold of function. And really, to really hit the target hard, and block not only B-cell growth, but also inflammatory responses, this is directly relevant for inflammatory response as well, is really key, and only targeted protein degradation can do that. So the other program we're developing, that this same paradigm that I'm showing for BTK, applies to IRAK4. So IRAK4 has a scaffolding function as well. That's been a noted, highly desirable target for inflammation for some time. Gilead, we're pursuing that with Gilead. They had been pursuing an IRAK4 inhibitor, and we've been benchmarked against that, compound and shown that the IRAK4 degrader has this kind of, potential additional function through the scaffolding effect. So this is very, very, important and central to hitting a target. The third inflammation target that we're working on at Nurix is STAT6. Now, this is a very different target. This is a transcription factor that's on the degradation pathway. This is we're pursuing with Sanofi. And as a transcription factor, really, inhibitors have not been, in general, successful against transcription factors in general. Now, the STAT6 degrader, we think, is gonna be the superior approach. People have made inhibitors to STAT6 as well, but again, same story, that you're taking out the total function of the protein with a degrader versus an inhibitor, which we think is a superior approach. Excellent. Excellent. And any foreseeable milestones from the collaborations with Gilead or Sanofi that we should be anticipating? I know that you've set up nicely those inflows as certainly supportive to the resource positioning. Yeah. So, we have several programs in the Sanofi and Gilead alliance, and as well as the Pfizer Seagen- Sure ... I... I should mention, too. Sure. And so we have milestones all along the discovery, drug discovery pathway, and we announce those in aggregate. I'd say, you know, quarterly, we've been hitting milestones. Yes. I think last year was over $100 million brought in through across all of our three partnerships, so a lot of non-dilutive capital- Mm-hmm ... distributed across various payment forms. But the, I think the ones that most people are watching going forward would be announcing new development candidates. Yes. So the IRAK4, for example, was last year with Gilead. We anticipate additional development candidates with our partners. We haven't given the timing for those, but those would be the things to look at. And then at that time, in general, we specify, as we get close to the development count, we specify the target. So the STAT6 was recently announced with Sanofi, for example. Yeah. Okay. And just given these existing collaborations and what we know is coming, what could come, as you're mentioning with these candidates, does Nurix have an interest in additional partnerships? The plate seems full, but that's just from my perspective. How full is the plate, or is this really a greater emphasis on what you're saying is getting the most out of what you already have? Well, so I do wanna talk about our degrader antibody conjugate program- Yeah ... because I think this is an area that there could be future partnerships. This is such a huge potential area. So what we're doing here, and pictured on the lower left, is we're using a degrader as a new payload for the antibody. So traditional ADCs, which have been very successful drugs, the payload is generally a toxin, and here we're using a targeted protein degrader molecule, which gets into the cell via the antibody and can knock down, knock out specific proteins and deliver this, you know, anticancer effect without this general tox issue, which has been an issue for ADCs. So as these degrader antibody conjugates, or DACs, as this concept, I think, grows, I think we'll see it grow like we've seen the ADC field grow. Mm-hmm. Right? So this is an area of much great potential, future growth in terms of partnership, and technology. And it's, it also demonstrates just the sheer versatility of the degrader concept. So now there's plenty of room for more partnerships, you know, with Nurix. Mm-hmm. And we have our own wholly owned pipeline, for example, too, which I think could also be involved in partnerships. But our technology and our platform is really so broad that yeah, future partnerships are definitely part of the picture. Sure. Excellent. Just in the interest of time, you did mention Cbl-B and 1607. Just remind us of the mechanistic basis there and where you are with the clinical progression there? So that is the exact opposite- That's right ... of target approaching degradation, where we're inhibiting an E3 ligase, Cbl-B, very specific E3 ligase... and that raises protein levels. Yes. That is in phase 1 across 11 different solid tumor indications. We have talked about a clinical update later this year, and that, that's really where that program is. Very exciting, new targets. It's immuno-oncology target, very well recognized scientifically as a target and genetically. We're the first-in-class Cbl inhibitor, and, and so we're, we're really breaking new ground with there also. Great. Arthur, we'll leave it there. A A lot going on with Nurix. We look forward to the updates coming up soon this year. Great. Thank you very much, Greg. Thank you. All right. Thanks, everybody. Bye. Healthcare conference. My name is Greg Renza, one of the biotechnology research analysts here at RBC, and we're pleased to have Pulmocide with us today. Giving a presentation from the company is the CEO, Dan Burgess. Dan, over to you, and thanks for joining us. Hi, Greg, and thanks to the RBC team for having us here today. Appreciate the opportunity to present to you about Pulmocide. We're a little bit unusual as a private company that we've managed to advance our lead asset into phase 3. We're a respiratory company focused on immunocompromised patients with a condition known as aspergillosis. It's a fungal infection. We'll talk a good bit about that as we go through here, and we're really looking at both treating and preventing aspergillosis infections, both acutely and chronically, so a broad base of indications we can go after. The drug itself was. It was invented by our scientists in-house, the former heads of the respiratory group at GSK and had decades of experience developing inhaled drugs. They came to the realization that in the Aspergillus space, an inhaled drug is really what was needed here. So it was purpose-built to be given as an inhaled agent. I think the best evidence for the fact-