Nurix Therapeutics, Inc. ($NRIX)

Welcome to the Nurix Therapeutics, unlocking the full potential of back stack call. [Operator Instructions]. I would now like to turn the conference over to our host, Arthur Sands, President and CEO. Arthur, you may begin.

Thank you very much, and good day, everyone. I'd like to welcome everyone to our call today for a discussion around a very important new collaboration between Nurix and Roche centered on the development and commercialization of bexobrutideg, our potentially best-in-class BTK degrader for B-cell malignancies and autoimmune disease. We will be making certain forward-looking statements today, so I refer you to our disclaimers and risk factors which we have filed with the SEC. So today, I'm very delighted to be joined by our Chief Financial Officer, Hans Van Haute our Chief Business Officer, Jason Kanter; and our Chief Commercial Officer, John Northcott, on this call. And we prepared a short presentation for you on the strategic underpinnings of this new collaboration as well as some of the details regarding the structure of the partnership and the planned drug development initiative and most importantly, the potential value creation for patients as well as for all Nurix and Roche stakeholders. After this presentation, we will have time for a question-and-answer session. So first off, I'd like to make a few general statements about the collaboration we're announcing today. It unites 2 companies on a common mission to unlock the full potential of a next-generation BTK targeted therapy, bexobrutideg, or Bexdeg for short. Bexdeg is a potential best-in-class BTK targeted therapy that specifically and potently removes the BTK protein through targeted protein degradation. Bexag has generated robust clinical data in a broad CLL patient population that is chronic lymphocytic leukemia as well as in selected NHL or non-Hodgkin's lymphoma indications and has also generated compelling preclinical data n other therapeutic areas, including chronic spontaneous urticaria or CSU and multiple sclerosis or MS. The collaboration combines Nurix leading position in targeted protein degradation, with Roche's established leadership position in oncology, immunology and neurology, thereby unlocking opportunities across multiple therapeutic areas. Specifically, Roche's existing portfolio of B-cell targeted therapies creates the potential for synergy with Bexdeg's ultimate therapeutic targets in both CLL and NHL. Further, Roche's well-established product franchises of Solar and allergy and immunology and OCREVUS and MS create even broader potential for exploration of Bexdeg's utility in additional major therapeutic areas. Lastly, Roche's global clinical, regulatory and commercial infrastructure can help make a shared ambition vision for Bexdeg's reality, namely developing Bexdeg as a potential backbone therapy across BTK mediated diseases to be available globally for patients in need. With that framing, I'd like to turn the call over now to Jason, our Chief Business Officer, who will walk you through the financial structure and strategic rationale of the partnership. Jason?

Great. Thank you, Arthur. It's truly a pleasure to be able to announce this transformative partnership between Nurix and Roche. Today's announcement marks the culmination of a very comprehensive and competitive process, which we believe maximizes the clinical and commercial opportunities for Bexdeg across oncology, immunology and neurology. Importantly, this global partnership provides Nurix with a clear path to achieving its corporate strategic goal to become a fully integrated biopharmaceutical company capable of bringing novel to greater based medicines to patients in major medical markets. The deal terms also represent a milestone in the field as it is one of the largest, if not the largest deal of its kind for a degrader drug, which we believe is emblematic of the tremendous potential that Bexdeg and targeted protein degradation in general, hold for medicine. Following the close of this transaction, Nurix will receive $700 million in upfront cash with total potential payments of up to $2.3 billion, inclusive of the upfront. This includes clinical, regulatory and commercial milestones, both aimed at rewarding success and also time to provide offsetting funding scaled with our robust clinical development plan and its associated costs. Importantly, additional significant value beyond the $2.3 billion comes from the future retained downstream economics captured in the 50-50 cost profit share in the U.S. as well as royalties on ex U.S. sales. which make this deal potentially extremely value-enhancing for Nurix, both in the near term and over the long run. Nurix and Roche will co-develop Bexdeg globally across indications, leveraging the robust clinical plan already underway at Nurix and expanding our operational footprint with Roche's global development and regulatory capabilities. Development costs will be shared 40-60 with Nurix paying 40% and Roche paying 60% of global development costs. Beyond the dollars, the structure reflects a true partnership, a shared mission and a vision to maximize the value of Bexdeg across multiple indications with shared U.S. commercialization and Roche taking on operations of ex U.S. commercialization. Driving the significant financials and the chosen structure of the deal are the compelling attributes of Bexdeg a potential best-in-class BTK targeted agent. First, BTK has proven itself to be a foundational target and a central node in controlling B-cell and other immune cell activity with proven therapeutic utility across a wide range of diseases including in oncology, immunology and neurology. The potential advantages of Bexdeg are numerous and derived from its unique mechanism of action. Unlike inhibitors, Bexdeg removes BTK from cells, eliminating both the enzymatic and scaffolding functions of BTK, a much more profound blockade of the BTK signaling potential. Bexdeg acts catalytically. A single Bexdeg molecule can remove approximately 10,000 BTK proteins per hour from the cell, increasing its potency and fundamentally changing the PK/PD relationship of a small molecule drug to its target. Bexdeg has also been engineered to be exquisitely selective, which we believe accounts for its highly favorable safety profile. In the oncology setting, Bette also has a unique advantage of addressing the widest range of BTK mutations overcoming treatment resistance and driving deep and durable responses. And finally, Bexdeg has demonstrated clear ability to cross the blood-brain barrier, bringing demonstrated clinical benefit in CLL and lymphoma patients whose disease either originated in or spread to the brain. This demonstrated activity in the brain, we believe also has the potential to translate into significant clinical benefit for patients with multiple sclerosis. The mechanistic advantages of Bexdeg have translated to clinical benefit for patients, which became apparent at the earliest stages of clinical development. In fact, we believe the results of our Phase Ia trial are actually quite remarkable. For patients with chronic lymphocytic leukemia, or CLL, Bexdeg tag provided a robust 83% objective response rate in a patient population that has already received a median of 4 prior lines of therapy. This high level of clinical activity is observed across patients with high-risk features such as BTK mutations associated with resistance to BTK inhibitors and other high-risk molecular features as well as for patients with CNS involvement. And these responses are quite durable. In our Phase Ia dose escalation experience, the median PFS is 22.1 months, which appears to exceed existing therapies especially considering the degree of prior treatment that these patients have received and the fact that they have been treated across a range of Bexdeg doses. For my last slide, I want to share with you my excitement for Roche's partner. I really can't think of a better partner to maximize the opportunity for Bexdeg to deliver benefit to a wide range of patients. On every axis, scientific, clinical and commercial, Roche is the clear leader and the best partner for Nurix. Roche is an innovator in the area of B-cell biology, not only in oncology, but across indications, including immunology and neurology, with blockbuster standards of care, including Rituxan, Gazyva, Ocrevus, Venclexta, Polivy, Xolair and emerging new bispecifics and of course, their BTK inhibitor ibrutinib. We are extremely excited by the shared vision and enthusiasm for bringing best egg to patients across indications and to position Bexdeg as the best in category agent across disease setting. When we embarked on this partnering process, we wanted a partner who shared our scientific conviction who had deep disease expertise across oncology, immunology and neurology and who had the infrastructure to take bexobrutideg global. Roche checks every 1 of those boxes. To tell you more about our development plan, I would like to turn it back to Arthur.

Thanks, Jason. Before I dive into the development plan, I just want to mention that it's exciting as today's announcement is this collaboration really is ultimately about something much bigger and that is our mission and now our common mission with Roche, which is to establish the greater base medicines at the forefront of patient care. What makes this collaboration so important is that it gives both Nurix and Roche, an opportunity to fill that mission on a very large scale. Together, Nurix and Roche have aligned around a shared goal, advancing bexobrutideg into areas of significant unmet medical need, where we believe it has the potential to make a meaningful difference for patients. So let's turn to the joint development plan more specifically. So importantly, this is not a collaboration centered on a single indication. It is a comprehensive development strategy designed to explore the full potential of bexobrutideg across oncology, immunology and neurology. The result is a broad clinical development plan that we believe can maximize the value of Bexdeg while creating multiple opportunities to improve patient outcomes. The breadth of what we are pursuing together across 3 distinct therapeutic areas reflects the potential effects of the Bexdeg mechanism of action to counter disease biology and the significant unmet medical need that persists in these major disease categories. In CLL, patients continue to develop resistance to current BTK inhibitors as well as to other difficult-to-treat genetic driver...

Operator, did we lose Arthur?

His line is connected but not hearing any sound. He may need to reconnect.

Okay. Well, I'll just pick up where he left off and Yes. Okay. In CLL, patients continue to develop resistance to current BTK inhibitors as well as other difficult-to-treat genetic driver mutations. And once they do, options are limited. -- in immunology and neurology, BTK-targeted therapy has initially been explored with BTK inhibitors, leaving the additional benefits of total protein removal untapped. These are key motivators that fuel the ambition that Nurix and Roche share for this molecule. Let me walk you through an initial outline of the collaboration plan. Our overarching strategy is to advance a comprehensive exec development program across multiple lines of therapy as both monotherapy and in combination settings in B-cell malignancies. The first 3 studies are as Nurix has previously outlined and will continue as per their previously described designs and time lines. These include the Daybreak CLL 201 study for potential accelerated approval, the Phase III Daybreak CLL 306 study and the Phase Ib/II basket combination study. The Phase Ib/II basket combination program is designed to enable not only future planned first-line and/or second-line Phase III studies in CLL, but also potential Phase III combination studies in NHL as indicated by the blue bars below. Specifically in mantle cell lymphoma or MCL and Waldenstrom macroglobulinemia or WM. We are pursuing both on therapy approaches for speed to market and combination strategies to enable potential fixed duration regimens with Roche's venetoclax as well as exciting potential for multiple other combinations with Roche's other existing portfolio drugs. Overall, one can easily imagine how this powerful collaboration with Roche can establish bexobrutideg as a future backbone therapy across B-cell malignancies. I think, Arthur, are you back, Arthur?

I am back. Can you hear me?

Yes.

Yes.

Okay. Great. All right. Sorry about that. And Jason, thanks for taking up. So yes, as we -- I'd love to speak to this next slide here about CSU and MS. And so let me just dive into that. We see these as really representing very significant expansion opportunities. And I would like to spend some time walking through some of the rationale, both scientific and clinical for expanding Backstage clinical development into these areas. So first, the totality of the BTK protein, not just the kinase function plays the key role in autoimmune disease biology particularly as a critical regulator of the Fc receptor activation of mast cells and spills and controls B-cell inflammatory pathways Secondly, we have shown that Bexdeg more potently suppresses BTK signaling and activation in mast cells, basophils and B cells compared to multiple BTK inhibitors in vitro, and third, we have recently published our finding that Bexdeg achieves rapid, robust and sustained degradation of BTK in both the skin and the blood of healthy volunteers. Therefore, we are actively planning with Roche the initiation of a Phase II clinical trial in chronic spontaneous urticaria to determine the dose of Bexdeg required to deliver the full potential of BTK degradation to treat this disease and enable a Phase III program as rapidly as possible. Turning to neurology and MS. We know from our current trials that Bexdeg crosses the blood brain barrier and exhibits therapeutic activity in primary seamless lymphoma and CLL with CNS involvement without signs of liver toxicity and a safety data set of greater than 300 CLL and NHL patients to date. In addition, Bexdeg has demonstrated potent therapeutic activity in preclinical disease models of MS. And perhaps most excitingly, we have shown robust in vivo degradation of BTK and brand resident Microglia in animal models, eliminating both the kinase and scaffolding functions of BTK and thereby providing a mechanistic rationale for potentially enhanced biologic activity in the brain with direct implications for diseases such as MS, based on the above rationale, we are also actively planning with Roche, a Phase II clinical trial in MS, and we cannot think of a better partner to be joining forces with to explore the exciting potential of BTK degradation in neurologic disease. So overall, for Nurix, this is a defining moment. This collaboration enables and accelerates our evolution to become a fully integrated biopharmaceutical company, one that combines an industry-leading targeted protein degradation drug discovery engine, with the ability to translate innovation into global clinical and commercial impact across multiple therapeutic areas We have an innovative oncology pipeline spanning both hematologic and solid tumors, both wholly owned and partnered with significant product sharing rights across multiple indications. In addition, we continue to push the forefront of targeted protein degradation technologies with our degrader antibody conjugate or DAC programs, a truly exciting area to be the subject of future disclosures. If we turn to our pipeline in immunology and inflammation, we can see that -- we are -- now have quite a breadth of platform that beginning to translate across entirely new therapeutic areas, particularly in immunology and neurology. Nurix's opportunity for value creation is poised to continue to grow substantially as both our IRAK4 program with Gilead and our STAT6 program with Sanofi continue to advance in development. These also will be the subject of future important clinical and business updates. With that, I'd like to hand the call to John Northcott to discuss the commercial implications of today's announcement. John?

Thank you, Arthur. Good morning, everyone. I'm John Northcott, Chief Commercial Officer of Nurix. I will open with saying how thrilled I am that we are announcing our partnership with Roche, the right partner, to help us execute an expansive clinical development plan for Bexdeg across CLL, NHL, CSU and multiple sclerosis. Our joint development plan targets these indications, both as a monotherapy and in combination as appropriate to unlock the power of protein degradation in advance the standard of care for patients. Across range of therapeutic areas, all of which have very large addressable patient populations. Each of these therapeutic areas and markets have the potential to generate significant value and represent major blockbuster potential for Bexdeg, with a collective total initial addressable market opportunity of approximately $48 billion. We believe this partnership with Roche positions us exceptionally well, bringing proven commercial infrastructure, deep therapeutic area expertise and established market access across every indication we will pursue together. This is a real competitive advantage. And it means we are in the strongest position to deliver innovative therapies for patients across all of these areas, which is ultimately what drives us. Needless to say, these are all large competitive markets and the established global footprint of Roche will rapidly enhance our ability to deliver Bexdeg to every major market. First, in terms of expanding our clinical development program into new countries with a greater number of investigative sites and then towards achieving regulatory approvals and launches across the globe. Under the terms of this global agreement, we will build our size of the ability to support a successful launch of Bexdeg in a stage appropriate fashion. With the benefit of Roche's established infrastructure behind us from day 1. Giving Nurix a clear path to becoming a commercial stage revenue-generating and ultimately profitable company. Today marks a new chapter for Bexdeg and Nurix, and I'm confident that together, we will achieve great things for patients and all the stakeholders we serve. Now for a brief look at the high-level financial implications of this strategic collaboration. I will hand the call to Nurix Chief Financial Officer, Hans Van Houte. Hans?

Thank you, John. Well, as most of you are aware, for more than a decade, we've built 1 of the industry's leading targeted protein degradation platforms. And we've also used that platform to establish partners with some of the world's leading pharmaceutical companies. These collaborations have generated over $1 billion of nondilutive cash generics, while enabling us to retain meaningful co-development, co-commercialization participation and future success of our programs. This Roche collaboration represents the most significant example of that strategy to date. It brings a potential best-in-class BTK degrader together with a global leader in oncology, immunology and neurology, to expand the development and commercialization reach of bexobrutideg while preserving substantial long-term economics for Nurix through U.S. profit sharing and ex U.S. royalties. Importantly, this transaction also significantly starts our balance sheet. Following the receipt of the upfront payment, Nor will have approximately $1.24 billion in pro forma cash, providing substantial resources to advance bexobrutideg in multiple indications, invest in our wholly owned pipeline and continue to invest in our targeted protein degradation platform. More broadly, this collaboration reinforces the model that has served us well, leveraging our drug discovery engine to create innovative medicines, partnering strategically where accelerates development and maximize patient impact and retain meaningful participation in the value we create. Back to you, Arthur.

Great. Thank you, Hans. Before opening the call to your questions, I'd like to briefly summarize some of the key points and implications of today's announcement. So first of all, in collaboration with Roche, we are establishing a multi-indication multi-therapeutic area, clinical development program for bexobrutideg in malignant hematology, immunology and neurology. Next, within malignant hematology, we are broadening and accelerating Bexdeg's clinical development program not only as monotherapy but with combination regimens enabled with Roche's significant portfolio of innovative therapies for B-cell malignancies. Indeed, the initiatives within this collaboration positions Bexdeg as a potential backbone therapy across BTK-driven diseases. Together, Nurix and Roche bring synergistic scientific, clinical and commercial capabilities that are creating a shared economic opportunity across the projected $48 billion addressable market. Enabling all of this is bexobrutideg, a real stallion of a molecule that reflects years of scientific innovation and demonstrates the power of targeted protein degradation to fundamentally change how we intervene on disease biology. With Roche, we have the right partner, the right resources and the right plan to bring bexobrutideg to patients globally across multiple diseases in multiple geographies. I hope today we have presented and you can also sense from my overtly positive tone, a more expansive picture of what Nurix is and will be. a multi-asset, multi-indication company with the scientific foundation, financial resources and strategic partnerships to compete and deliver as the highest level of drug development and commercialization. So with that, we'd like to open the call to questions. So operator, if you could do that, please, we'll stand by.

[Operator Instructions]. Our first question comes from Brian Abrahams from RBC Capital.

Congratulations on the partnership. I was wondering if you could maybe elaborate a little bit more around the expected additional expansion of the Bexdeg development plans and as well as some of the specific combos that you may pursue and I guess, is there any rationale around potentially further expanding the ongoing and planned CLL studies just given the bolstered resources that the deal brings.

Sure. I'll take that. So yes, we have plans to expand -- let me first address the combination portion of the question. We are initiating as planned, our Phase Ib/II study which is a basket study, starting with CLL, but also can incorporate NHL indications and anticipate multiple combination drug partners. One of the primary ones we're starting with there is, of course, another clock, which is key for Roche as well. So that would be an all-oral combination. But we are also -- we have also outlined cohorts that will allow for anti-CD20 antibodies to be incorporated into cohorts this will start in second line patients, but then also can then be upgraded after the initial combination results are obtained into first-line cohorts, which we will then choose combination agents at that time. In addition, as you can imagine, with Roche's portfolio, this combination basket study could be expanded quite substantially, we've not yet outlined what those studies would be, but they are definitely on our radar. With regard to the monotherapy, we are wholly focused on initiating our Phase III program in the head-to-head study against pitibrutinib, that's Daybreak 306 CLL that is a study anticipated to be at approximately 600 patients, as we previously outlined. Nurix alone, we, of course, outlined, I think, many countries involved, primarily Europe, U.K. and U.S. With Roche, we are now actively expanding that geography. We'll have to stay tuned for that, but that's going to be something that I think will definitely accelerate our program overall and establish a truly global footprint, making bexobrutideg, of course, even more of a competitive agent. So I think with that, I believe I've answered the bulk of your question.

Our next question comes from Tess Romero from JPMorgan.

Thanks for all the detail you provided as well. So what color can you give us on how this collaboration came to pass and the process that it seems that you ran? And second question from us, just double-clicking here from a housekeeping purposes. Can you give us a picture of how the upfront cash and future milestones will be accounted for as we are thinking about our models?

Okay. Let's start off with the first part, Jason, would you please take that? And then we'll go to Hans when you're finished.

Yes. Thanks, Tess. So yes, indeed, this was a competitive process. We had many players who had an opportunity to take a look at the asset. And in fact, many who have been tracking it for quite some time. The deal itself was driven largely by our ability to show very robust clinical data, not only in terms of ORR, but of course, in terms of PFS, our clearing of the 600-milligram dose through Project Optimus and the differentiation data that we were able to show last October, which I think positions bexobrutideg is a potential best-in-class BTK degrader. Hans, do you want to talk about the accounting?

Yes, sure. Yes, we're currently evaluating the accounting treatment of the transaction. We'll provide additional detail in the future SEC filings and earnings communications. Thank you.

Our next question comes from Gregory Renza from Truist Securities.

Congratulations on the deal. Arthur, you certainly talked about maybe expectation of subjects of future disclosures when it comes to your pipeline. You mentioned DAC and certainly on the I&I I'm just curious from here when it comes to at Nurix's wholly programs, which ones are you most excited about? Which one will perhaps provide the most opportunity for you? And for investors? And then maybe just one specifically. I'm just curious how you're thinking about the Panretigrader program from here. You certainly mentioned maybe this and others as future topics.

Sure. Well, thank you. So I believe an investment in Nurix is really an investment in the totality of our pipeline, not necessarily any one program, although I think many investors may have their favorites. And certainly, Bexdeg is our leading asset with with one of the greatest potentials. But I'd say looking at the totality of our pipeline because we have not only our wholly owned assets, but our partnered portfolio, which now includes partnerships with 4 major corporations. The -- of course, the one we're discussing today is the largest to date this -- each of these partnerships allows for us to participate in cost profit share agreements with each of the partners. Obviously, Bexdeg be detailed at a 50-50 in the United States, which is quite a substantial product right opportunity. And then across the 3 others, we have a total 6 such option rights, those are structured as options after human proof of concept for significant cost profit shares as well in a similar fashion. So you're looking at a diversified portfolio and significant product rights owned by Nurix across multiple drugs, which I think helps derisk the investment thesis as well. Now in addition to that, we have additional wholly owned -- currently wholly owned projects, NX607, I personally think is extremely exciting as new immuno-oncology agent. It's a civil B inhibitor, which has been developed through Phase Ia and we look forward to Phase Ib as the next step for that agent. We have additional projects. You mentioned our Pan-braptograder, which is a new entrant into our pipeline. -- for that it can address basically any of the BRAF mutant resistant mutant clones -- and then we have new agents within our I&I portfolio, which are undisclosed. And then, of course, our DAC portfolio. So again, I see it as a holistic investment, including not only our wholly owned pipeline, but also these terrific co-co development options across program, 7 programs total now. So thank you for your question.

Our next question comes from Terence Flynn from Morgan Stanley.

Great. I guess I had 2 is the first is just -- can you confirm if Roche is aligned with you on the accelerated approval path for Bexdeg and CLL, I assume so, given the prepared remarks, but I just wanted to check that. And then on the immunology side, very interesting to see that more on the Phase II plans there, what do you think the earliest is we could see some initial proof-of-concept data from those 2 trials?

Sure. So thank you for your question. So first, on the first point, yes, we are aligned with Roche on the accelerated approval pathway that being the day break 201 study, CLL 201, which is underway. That is in a fourth line patient population post pitibrutinib patients. And then to your second point, in terms of when we would first see data from these, so I think we need to go stepwise, which is, first, we're committed to initiating the trial. So we're committed to an IND focused on CSU in the second half of this year. We are actively, as I mentioned, actively working with Roche on the design of that trial and implementation as well as for the MS trial, we've not specified a time frame for initiating that. But I would say that upon initiation and getting those trials underway, then we could make a better forecast with regard to data. So I'd like to defer that part of the answer.

Our next question comes from Biren Amin from Piper Sandler.

Congratulations on the partnership this morning. Can you maybe just talk about your read-through on Roche's ability to take the fenebrutinib development playbook in CSU and MS and to kind of apply those learnings to the Bexdeg program. So that's the first question. And then second question, Roche clearly has a significant diagnostics franchise and have novel the test for MRD that suggests higher sensitivity for MRD. Could you maybe talk about how you're planning to pair those diagnostic tests for the CLL and NHL development for Bexdeg?

Thanks, Biren. So yes, I think, first off, on your first part of the question, there's no doubt that Roche's expertise in CSU with their extensive solar franchise is really the market leader on their understanding of the underlying disease biology and their general experience overall in allergy and immunology is going to pay dividends for the setup of the Bexdeg Phase II trial in CSU. So many of the learnings that they have, I'm sure, will be put into play here with this next step and we've really valued our initial meetings and planning sessions with them on that topic. With regard to pirtobrutinib in MS, there's no doubt that Roche has the most relevant recent experience completely in -- and while inhibitors like kinobrutinib work by temporarily blocking the kinase activity of the BTK protein, I think the fact that bexabritodeg physically eliminates the BTK protein removing both its kinase functions and scaffolding functions. These 2 distinct mechanisms of action against the same target will -- has the potential to really maximize the ability to address the complex neurologic indications like multiple sclerosis and may ultimately provide more diverse and optimized treatment options for patients with MS. So there, again, I think -- and of course, it's not just pedaburtinib but the OCREVUS and their entire franchise is really still powerful here. Again, we're going to be in a very strong position to optimize that Phase II trial in MS and we very much look forward to that. So I gave a little bit of a long-winded answer there. But the second part of your question, again, could you remind me?

Yes. Second part of the question was around the diagnostic franchise that Roche has. And specifically, at AACR earlier this year, they unveiled a new novel MRD test that suggests higher sensitivity in testing. So a way of potentially deploying that into the Bexdeg CLL and HLL development plan?

Yes. So we've had some initial discussions on the biomarker topics in general and Roche's advanced technologies there and their experience base there, not only in CLL, but also in MS. So yes, we're very much going to be engaged with them on bringing the absolute latest technology diagnostic/experimental biomarker technologies into these trials. I think that's going to be a big advantage as well. Thank you for bringing that up. And thanks for your question.

Our next question comes from Roger Song from Jefferies.

This is Nabil on for Roger. Congratulations on all the updates and on the partnership. I have 2 questions from us. So one on the -- just a little bit more if you could speak on the differentiation of Bexdeg in MS, where you have seen inhibitors have liver liabilities? And then just that CNS penetration, if you could comment a little bit more on that. And then I had a follow-up.

Sure. So the advantages of Bexdeg in MS are based on some of our observations that we've already seen in the clinic in CLL and primary CNS lymphoma. So they're not just theoretical. So they are, number one, clear access to the brain with biologic activity that has translated to clinical responses for patients with really significant brand disease. That's, I think, quite important. Then there are the also observations of how important both elimination of the kinase function and the scaffolding function are in the CLL setting, and we've demonstrated evidence that those same dual functions are important in autoimmune disease, and we would expect would read through to a potential efficacy advantage in diseases like MS and other autoimmune diseases. So we're translating -- we expect to translate those advantages of total removal of the protein into potential superior efficacy results in autoimmune disease. p The other aspect of this, which I think you alluded to with regard to safety, is that on the liver enzyme front, we've seen no signs of liver toxicities and now over 300 patients with CLL or NHL, all of whom who have essentially received multiple therapies, including multiple chemotherapies and various prior sources of potential liver insult. And yet we see a very safe liver safety profile. So we think that's extremely important and part of that, we believe, may relate to the lower drug levels in the blood that a degrader can operate at. So far lower hundreds to thousands of fold lower blood levels, achieving complete removal of the BTK protein. So the total drug burden in the system is lower and that may attribute to a much lower reduction of general off-target effects, which some of the inhibitors may suffer from. Of course, bexobrutideg is exquisitely selective in and of its own right to be proteomics and all the optimization we've had.

So I think we may have lost Arthur again. Can we go to the next question, please? You're back, Arthur.

Am I bac. Okay. Well, I was finished with my answer anyway. So question. And jump in, Jason, if I go off again.

Yes.

Our next question comes from Derek Archila from Wells Fargo.

Congrats on the deal. Maybe just 1 on kind of housekeeping for Hans on the R&D spend. you're running around like $80 million to $90 million a quarter. I presume the majority of that was betted related. So just kind of any thoughts on go-forward spend now with this deal and kind of the offset now that Roche will be taking on some of the development costs. And then just turning back to some of the questions we already heard around the wholly owned pipeline. But I guess what do you kind of think is the next key update for the wholly owned pipeline. And anything specific that you would point to over the next 12 to 18 months?

Yes, I'll take the first half of that. Derik, not -- I'm not providing any updated financial guidance today. We'll provide updated financial information and guidance in our regular SEC filings and quarterly earnings communications. -- but needless to say, this transaction significantly strengthens our financial position and provide substantial resources to advance our strategic priorities, though, combined with the development cost sharing we believe we're well positioned to execute on all of our planned clinical and research initiatives. Maybe turn that back to Arthur.

Yes. So yes, Derek. So in terms of future updates, so the future updates will continue to be centered on bexobrutideg, but I think also there are updates to be expected on the stat 6 program and IRAK-4 program, these are all, of course, under partnerships. And with regard to wholly owned pipeline, then we would expect I'd say, next updates on MX 607 and 2127 and our BRAF degrader and then any new disclosures around so far undisclosed targets within our pipeline. And I think some of those disclosures, we discussed potentially in the second half of this year, having those if we get -- if we're able to get scheduled the corporate update day, corporate research date, it would likely be in the fall and would cover a greater degree of information around the newer wholly owned programs. Thank you.

Our next question comes from Stephen Willey from Stifel.

Congrats on the transaction. So I guess maybe just 2 quick questions. So curious if this transaction and the 40% commitment on global development spend now changes at all the decision-making process around some of the other -- the other opt-in decisions that you're presumably going to need to make here on some of these other partnered assets. So I guess that's kind of a bandwidth and resource question. And then just secondly, wondering if the agreement at all contemplates some freedom to operate around your ability to make future disclosures going forward? Or should we expect, I guess, the next 6 to 12 months of Bexdeg related catalyst to now maybe look a little bit differently post this deal?

Thanks, Steve. So I'll take the first part of the question and then hand the second to Jason. So on the first part of your question, with regard to our future options, which would encompass the IRAK-4 program with Gilead and the STAT6 program. with Sanofi. I do think that our financial resources are expanded at this point under this collaboration. This new collaboration we're announcing today and our financial commitments are bolstered then with our partner, Roche, that does create greater financial flexibility, but I would say this, we're going to have updates, as I mentioned, in the second half, and we anticipate those around the STAT 6 program, first likely and then the IRAK4 program. STAT 6 is clearly, I think, in terms of future option potential, our top priority program. I think for many reasons, IBC would then be our next priority. So I think we'll just have to stay tuned and see how those evolve and what the exact timing of those options are likely to be. So again, I think I'd like to defer to the second half to give hopefully, more clarity on updates on those programs. And then to the second part, Jason, could you address that?

Yes, sure. So there are a couple of parts to that question. So first on the cadence of disclosures around Bexdeg, I don't think you should expect it to change. We're still on this sort of [ HA ASH ] June and December disclosure time line. In fact, as soon as we get off this call, many of us are getting on planes and going to Stockholm to present the latest Bexdeg data at EHA. That will include an update to both the Phase Ia and Ib, including in patients with earlier lines of therapy with very robust ORR. So that is a new disclosure, which will be happening on Sunday. And in terms of our ability to provide future updates, the collaboration has a joint governance, which really has us in a very good position in terms of our ability to continue to advance the program and to be able to continue to provide updates as necessary to investors. So I don't think you should expect any change. In fact, you'll probably hear more about Bexdeg because now it will not just be us talking about it, but it will be Roche. And you saw this morning, they put out their own press release, I assume that at future medical meetings. This will be a program that's highlighted in their investor decks. And so we think actually the cadence and the volume of disclosure is going to increase as a result of the deal.

Our next question comes from Sudan Loganathan from Stephens.

Great. Congrats on the news here and great to see this collaboration come through. My first question is on the economics for the other indications outside of CLL. Do you anticipate them to be very similar with Roche or be on a case-by-case basis there? And then secondly, for John Northcott, just curious on what the commercial strategy is now for Bexdeg, there's been any changes yet or if there will be maybe as the conversations with Roche go on and the Bexdeg program advances.

Great. Jason, do you want to take the front part and then John.

Yes. So this is a Bexdeg deal. And so we are partnered globally across indications and the economics are fixed regardless of the indication. So we will be 50-50 cost profit sharing with Roche across indications as well as 40-60 development cost sharing across the indications. So there is no difference. John?

Great. Thank you, Jason. Yes. So once the deal closes, we will be forming a joint commercialization committee with Roche, where we'll be forming kind of our commercial strategy as well as our tactical and operating plans. This is going to be a wonderful opportunity. Roche will take the lead on the ex U.S., and we'll be working collaboratively here in the U.S. to execute the Bexdeg commercial strategy. for the benefit of patients.

Our next question comes from Jeet Mukherjee with BTIG.

Congrats on the partnership. So Roche in their press release noted that they saw Bexdeg as a potential best-in-class BTK degrader. Was just curious if you had any perspective or insight from your discussions? What they saw about Bexdeg's profile that made it a best-in-class degrader in their view. And then as a separate question, with Bexdeg now partnered, does this change what you plan to do or what indications you may want to go forward with when it comes to zalabrutamide?

So for the first part, I mean, I might share the answer with Jason because Jason, not only had orchestrated the deal process, but also the incredible diligence process associated with this deal. But I think -- so I'll answer on a high level, I believe that Roche having done their incredibly thorough homework have seen the efficacy profile and safety profile combined based on all of the clinical data we have to date to define it as this potential best-in-class agent. So efficacy and safety being, of course, the key parameters anyone would evaluate and besides the general statement, again, the level of diligence done, what they've seen and they've seen just about everything anybody could see with regard to Bexdeg. But Jason, do you want to elaborate any on this?

Well, again, I think it's really just part of the shared vision that we have. We have been saying, we believe we have best in class. We've brought some receipts as it relates to some of the preclinical data that supports that claim, not only differentiating us from the inhibitors but also from other degraders and like Arthur said, not only were they able to really do a deep dive and scrub our data internally, but we assume they've looked at others as well. So very excited that they are adopting that position. yes, and we agree. And then in terms of zelabrutamide, this is -- this drug is not included in the deal. However, it would not be our intention to compete directly with baxabrutideg with that molecule. So any advancement of that would be in indications other than those where we are moving forward with bexobrutideg, which is our highest priority.

Our next question comes from Brian Skorney from Baird.

Congrats, Jason, on this really a great deal can imagine about our partner in the B-cell landscape. You did spend a decent amount of time discussing the MS side of the story. And Roche had some interesting dynamics here, obviously, with the top MSeing drug right now. and are now submitted BTK in fenebrutinib. So I guess just given kind of the developments in the class and the liabilities among the covalent non-covalent and there's targeting MS. Do the companies believe that should be able to drive efficacy across the range of MS patients. And I guess what I'm really getting at is kind of a weird question, Tom, to answer, but what do the companies see as the advantage of Beko and MS over your partners on BTK inhibitor, which, as I said, is under review. And then I don't specifically remember collaborations like this triggering a Hart-Scott-Rodino review. But are there any concerns about the overlap between Bexdeg and Fennobind MS on an antitrust basis? Is there any clearance needed from FTC or DOJ here?

I'll take the first part of that question with regard to kinobrutinib. I think that I think Roche and Nurix both, I think we both see advancing both of these compounds. Obviously, bexobrutideg a bit of a highly selective inhibitor. -- advancing a highly selective inhibitor and a degrader really serves to broaden the Roche portfolio, I believe, from their perspective. These are 2 distinct mechanisms of action against the same validated target, which will potentially maximize the ability to address very complex neurologic indications like MS, which have multiple stages as you intimated in multiple manifestations and patients. So ultimately, I think they'll have the best MS portfolio across the board, incorporating OCREVUS and potentially fenebrutinib in our drug. And I think it will be a very, very powerful portfolio. The distinct advantages that degradation brings, I think I've already mentioned, i.e., removing the entire protein. I believe also the fundamentally different PK/PD with low drug levels achieving such great potential efficacy. So there are going to be some clear distinctions that bexobrutideg will have, but it will likely be part of a larger MS armamentarium that is out there. But from our perspective, Nurix, we think it definitely has the potential to be even a best in disease in MS drug. And it's oral, certainly could offer efficacy across multiple stages of the MS disease. We have no reason to believe that it wouldn't. But this will all have to play out in the clinical development plan. So then the HSR question is not really in my league. Jason, any comments there?

Well, we don't want to speak for regulators, and this is all deals has to go through an HSR review and our anticipation is that the deal will close in the third quarter.

Operator, I see we're at the top of the hour, which I think was one of our goals to be finished by then. So if there are no further questions, operator.

There are no further questions at this time.

Okay. Great. All right. Well, I'd like to thank everyone for their participation. It's a -- great day for both Roche and Nurix, and we look forward to giving you future updates. Thank you very much. Bye-bye.

This concludes today's conference call. Thank you for attending.