Nurix Therapeutics Inc EHA Meeting Discussion Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Gil Blum - Needham & Company Inc. - Analyst : So a couple from us, maybe for Dr. Linton first, just to put in context, what are the potential benefits of achieving complete responses in CLL patients? Kim Linton - University of Manchester - Senior Lecturer and Honorary Consultant in Medical Oncology at The Christie NHS Foundation Trust So look, complete response in CLL is not that common. And as Dr. O'Connor already explained with the two cases that she presented, just achieving disease control with a reduction in the cytopenias, the reduction in organomegaly, improves patient's quality of life substantially. So complete responses will happen. I suspect when we've treated more patients, but I don't think that that's something that you need to be concerned about because what's very clear from the people that have achieved a partial response in this study is that they are deriving considerable clinical benefits. And I can give you many anecdotes from my own clinical practice of individuals who have literally turned their lives around and are currently living their best lives and they're in partial response. So don't be too concerned about that. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 16, 2024 / 1:00PM, NRIX.OQ - Nurix Therapeutics Inc EHA Meeting Discussion

Question: Gil Blum - Needham & Company Inc. - Analyst : Okay, very helpful. And just to verify, were there no dose reduction delays or discontinuations in the CLL cohort?

Question: Gil Blum - Needham & Company Inc. - Analyst : Okay, that's also very helpful. And in the waterfall plot, there's a single patient who has progressive disease, but he's still on therapy. Any details there?

Question: Gil Blum - Needham & Company Inc. - Analyst : Okay, again, very helpful. And the last one, I promise. Will further studies continue to include patients with CNS involvement, which is different than most studies in this space?

Question: Gil Blum - Needham & Company Inc. - Analyst : Thanks for taking our questions and congrats on remarkable data.

Question: Gregory Renza - RBC Capital Markets - Analyst : Great. Good day, Arthur and team. Let me add my congratulations on the excellent updates this weekend. And thanks for taking my questions. Arthur, maybe a question for Dr. Linton. Dr. Linton, you certainly covered some of the attractive attributes of 5948. I'm just curious if you could help us maybe prioritize or stratify some of those characteristics that you find to be maybe most clinically relevant as this could potentially slot in as a treatment option in your armamentarium, especially when it comes to the tolerability, the potential for extended durability, that rapidity of onset, as well as the mutation coverage. That would be great. Thanks so much. Kim Linton - University of Manchester - Senior Lecturer and Honorary Consultant in Medical Oncology at The Christie NHS Foundation Trust Thank you. There's quite a few things actually that stand out as making this a very-difficult-to-treat group. One is the fact that they've had so many lines of treatment. And that means that they're not necessarily, they don't necessarily have any further standard of care options remaining. So it would be clinical trials or no further treatment for these individuals without a drug like this. The other is that they're heavily mutated. So in other words, even if they did still have these drugs available, they probably wouldn't respond to them because they've got mutations at the binding site. And it's not just the BTK mutations that are relevant here. It's also things like the TP53 mutations, which I briefly alluded to in my presentation. This is a very common feature of CLLs. It's acquired over time. And it just basically means that standard therapies don't work. And this is where drugs like this are really coming into their own. The other factor is that this is such an elderly population. When you're reaching your late 60s and 70s, you can't tolerate standard chemotherapy. The toxicity profile is too great. So you have to have a drug that's easy to -- that you can tolerate, basically. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 16, 2024 / 1:00PM, NRIX.OQ - Nurix Therapeutics Inc EHA Meeting Discussion And the safety profile that we've seen with this drug is fantastic. It's better than the first-generation BTK, the coveted BTK inhibitors. It's even better than the second generation BTK inhibitors. So this has got the potential to, as Paula was saying a moment ago, to get people into remission and to keep them on drugs.

Question: Joe Catanzaro - Piper Sandler Companies - Analyst : Congrats on the data here. Maybe one first on dosing. I'm wondering if you think this drug class is associated with a classic dose-response curve. Your data doesn't seem to suggest that. The BeiGene data doesn't seem to suggest that. And I'm wondering if it's maybe more bell-shaped dose-response curve. And maybe for Gwenn, whether mechanistically that actually makes sense here for the degrader mechanism. Thanks, and I have maybe a follow-up.

Question: Joe Catanzaro - Piper Sandler Companies - Analyst : Great. And I know, Arthur, you just sort of said you won't comment on other company data, but maybe I could just ask slightly differently. So after the BeiGene presentation, the presenter was asked about the lipase and amylase increases that program was seeing and how that's something that's not observed with BTK inhibitors. If I understood the presenter correctly, they mentioned that preclinically the program saw macrophage infiltration into the pancreas. So maybe for 5948, can you maybe just speak to preclinically whether you've ever seen any indications of amylase, lipase increases, pancreatitis, so on and so forth?

Question: Joe Catanzaro - Piper Sandler Companies - Analyst : Okay, great. Thanks so much for taking my questions.

Question: Joel Beatty - Robert W. Baird & Co., Inc. - Analyst : Hi, can you grab some of the data? First question is for Dr. Linton. Where could a drug like this fit in your treatment algorithm? If the profile holds up, would it ultimately make sense to use it as a later-line BTK therapy or could it make sense to use it as an earlier line? Kim Linton - University of Manchester - Senior Lecturer and Honorary Consultant in Medical Oncology at The Christie NHS Foundation Trust Obviously, the data currently are in the relapsed and refractory setting where we are seeing remarkable results, so I clearly think it could have a potential place at this later stage. But I think increasingly we're recognizing the importance of gaining disease control early on. And so I think to try and prevent the emergence of some of these BTK mutations, it makes perfect sense to bring this drug to the frontline setting, either as monotherapy or in combinations. And I would be very excited to see it in that space. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 16, 2024 / 1:00PM, NRIX.OQ - Nurix Therapeutics Inc EHA Meeting Discussion

Question: Joel Beatty - Robert W. Baird & Co., Inc. - Analyst : Got it, great. And then last question is between now and starting a pivotal trial sometime in the next 18 months, can you discuss what the rate-limiting factors are to have that happen?

Question: Joel Beatty - Robert W. Baird & Co., Inc. - Analyst : Thank you.

Question: Stephen Willey - Stifel Nicolaus and Company, Incorporated - Analyst : Yeah, congrats on the data. Thanks for the update. I guess maybe for Arthur or for Paula, just curious as to whether or not the patients who'd be enrolled into the Phase 1b, I think you talked about generating an additional 80 to 150 patients. Could some of that data be leveraged into the registrational study for an accelerated approval purpose? I'm just trying, I guess, maybe understand the rationale for maybe generating another 150 patients' worth of data without necessarily having that data count towards some kind of regulatory data set as it pertains to accelerated approval. And then I just have a follow-up.

Question: Stephen Willey - Stifel Nicolaus and Company, Incorporated - Analyst : Okay, that's helpful. And then just with respect to the BTK degrader safety that we've seen thus far, and again, I know these are kind of still early days, not a whole lot of follow-ups, not a whole lot of patients, but I'm not sure if Paula or if Dr. Linton wants to comment based on her experience with the inhibitors, but it certainly looks like we haven't seen any instances of Afib yet with the degraders in the clinic. And just curious if you think that there may be something unique about the mechanism that perhaps circumvents some of the cardio tox that we've seen with the inhibitors today. Thanks. Kim Linton - University of Manchester - Senior Lecturer and Honorary Consultant in Medical Oncology at The Christie NHS Foundation Trust So I can just come in from the clinical perspective in terms of the safety profile compared to the early generation BTK inhibitors. So I was involved in developing ibrutinib from the beginning. I've developed zanubrutinib, acalabrutinib, pirtobrutinib, you name it. And one of the key considerations with drugs like ibrutinib is the attrition rate. So the number of people that come off study or drug treatment if they're being treated in standard of care because of toxicity, not because of lack of activity. And that is one of the major disadvantages of the early covenant BTK inhibitors. Now whilst the second-generation BTK inhibitors are safer undoubtedly and we're seeing less hypertension, atrial fibrillation and other cardiac events, we are still seeing them. And of course, in this elderly patient group where there's a lot of past medical history of cardiac nature, that's a real consideration. So having been involved in the BTK degrader program with NX-5948 again from the first in-human study, I've been very impressed anecdotally that this drug appears to be safer. And then looking at the numbers that we presented today, undoubtedly we are seeing less toxicity across the board. We're not having to support these patients in the same way that we have to do with the other inhibitor drugs. And I might just ask Paula to talk about whether there's something mechanistically that might explain why you're not seeing as much cardiac toxicity.

Question: Stephen Willey - Stifel Nicolaus and Company, Incorporated - Analyst : Okay, thanks for taking the question.

Question: Eric Joseph - JPMorgan - Analyst : Hi, let me also add my congrats on these data. Just in thinking about the upcoming Phase 1b expansion, I wonder if there are any changes to the entry criteria that you're contemplating. It's a very treatment-experienced patient set that you've recruited so far and that you're describing today. I guess, do you expect the median number of prior treatments to be consistent into the Phase 1b portion? And whether it's related to median prior lines of therapy or not, what are you anticipating as sort of the pace of enrollment of the Phase 1b? Any plans towards site expansion or something to facilitate that effort? Thank you.

Question: Eric Joseph - JPMorgan - Analyst : Okay, great. Thanks for taking the question.

Question: Sudan Loganathan - Stephens Inc. - Analyst : Hi, everyone, and congratulations on the progress in the strong data for 5948 program. So my first question is regarding the response you're seeing in the different CLL pre-treatment groups. Can you provide more insight into the response rates for the CLL patients previously treated with the covalent versus non-covalent PTK inhibitors? It seems like there were some PRs achieved with the post-covalent PTK treatment, but not much data for the non-covalent treatment patients. So just one subset have a better -- stick out as a better response to PTK degradation as post-treatment. And then additionally, there are only 26% of patients with prior non-covalent PTK inhibitor treatment in this cohort. Is that due to the result of a lack of use of non-covalent PTK inhibitors or lack of progression post the non-covalent PTK inhibitor or just the need for more patients in the trial?

Question: Sudan Loganathan - Stephens Inc. - Analyst : Got it, thank you. And my second question was going to be, if you thought of a combination trial to lower dose and enhance responses, but obviously you've answered that in the prepared remarks. But I want to dive deeper and wanted to ask if prior treatment and failure to any of the potential combo pairs could disqualify patients to get onto the combination trial that you may be opening. And does this help get BTK degraders to that earlier line of therapy for all B-cell malignancies? Or is this kind of just a strategy specific to CLL?

Question: Sudan Loganathan - Stephens Inc. - Analyst : Great, thank you for answering my questions. And again, congratulations on the progress.

Question: Matthew Biegler - Oppenheimer & Co., Inc. - Analyst : Hey guys, thanks for squeezing me in and congrats from us as well. Dr. Linton, maybe if you could just provide us a little bit more detail on the patient that had the grade 5 adverse event. I mean, this was new, right? Was this like a particularly beaten-up patient or did pulmonary embolisms happen quite frequently in this kind of demographic? Just any kind of details that you could provide would be great. Thank you. Kim Linton - University of Manchester - Senior Lecturer and Honorary Consultant in Medical Oncology at The Christie NHS Foundation Trust I might ask Paula to answer that question if you don't mind.

Question: Matthew Biegler - Oppenheimer & Co., Inc. - Analyst : Got it. And were any changes? Sorry, go ahead.

Question: Matthew Biegler - Oppenheimer & Co., Inc. - Analyst : Understood. Were there any changes implemented to the protocol in terms of inclusion, exclusion, or anything else to try to maybe mitigate this going forward?

Question: Matthew Biegler - Oppenheimer & Co., Inc. - Analyst : Great. Thanks a lot.