Zymeworks Inc. (ZYME) Earnings Call Transcript & Summary

Great. Well, thank you, everyone, for being here. I hope everyone is enjoying the conference. I'm Emily West, I'm a Managing Director in our Healthcare Investment Banking Group. And I'm joined today with the Zymeworks CEO, Ken Galbraith.

And we'll go ahead and start on the Zyme priority review announcement recently, and we're looking forward to the update in November. Maybe you can start off with kind of the key focus areas and opportunities as it relates to Zyme as well as how you think about the pipeline and the platform for the company?

Yes. Great. Thanks very much, yes. Thanks for the invitation to be here. Again, I said with respect to zanidatamab, we made a very key decision in 2022 to choose Jazz Pharmaceuticals as our partner of choice to help for the development and commercialization of zani in the territories to go along with our existing partner at that time, BeiGene in Asia Pacific region. And since we completed that deal at the end of 2022, we've been very pleased with the attention and dedication paid to zanidatamab from both Jazz and BeiGene. And we're quite pleased with the progress we are to date. Right now, we have regulatory reviews accepted on zanidatamab for second line Biliary Tract cancer in not just the United States, but also in Europe and most recently in China by BeiGene. So we're -- we've developed this bispecific antibody zanidatamab in the HER2 space from the very early days of the idea and the engineering and through development and bringing on Jazz has just allowed us to have the capital and resources to hopefully optimize the potential of zanidatamab in multiple patient populations. So besides the second-line BTC study, we have a first-line GEA study reading out top line before the end of this year, which is a bigger patient population, but also an area of great unmet need in the HER2 targeted therapy space. And beyond that, we also see Jazz investing starting in the second half of this year. And a pretty significant clinical development program to explore zanidatamab in the metastatic breast cancer setting. So I think Jazz and BeiGene are working with us to hopefully optimize the potential we saw on zanidatamab from the very first time that we engineered it. And you can certainly hear the excitement that Jazz has in their fireside chat. They did a little earlier today at the conference. They certainly you understand what that means to DAS's potential of how they can impact patients. And from a financial perspective, something that could eventually bring in peak sales of up to $2.5 billion was our guidance today into their oncology business. So really excited about the progress we're making with zanidatamab and getting it to market in conjunction with our partners in BeiGene. In the meantime, we've been spending the last 18 months focused on our holding on portfolio outside of the HER2 targeted space. And right now, we're right in front of the first of 5 INDs that we have planned for the next 24 months to bring that portfolio of novel antibody-drug conjugates and novel multi-civic antibodies into clinical studies, using the proceeds in the Jazz deal. And so we're really excited to broaden out the portfolio of our wholly-owned agents at the same time as progressing zanidatamab with Jazz and BeiGene.

Great. And maybe for the group reference, can you just remind us how do the economics and financials work with both Jazz and BeiGene? And how does that kind of change as you move forward with regulatory approvals?

Yes. So in addition to an upfront payment we received in 2022, which is the proceeds that we used to end up with a cash balance of $0.5 billion at the end of 2022 to finance this wholly-owned portfolio that we were now putting in the clinical studies. Jazz and BeiGene now took over all of the further development costs and obligations for zanidatamab that allows us to, to then allocate our capital to the remaining portfolio that we're trying to build. Beyond that, we're still entitled under our Jazz agreement up to $525 million in milestone payments based on regulatory approval of zanidatamab in different markets and different indications. And hopefully, that starts soon with BTC under regulatory review in the U.S. and other jurisdictions. And we -- on the commercial side, we're entitled to a royalty of between 10% and 20% of sales, depending upon annual net sales as well as another up to $900 million -- almost $100 million in commercial milestone payments. based on hitting certain sales targets. So we're certainly comfortable with the choice we made about partnering with Jazz to add to BeiGene and not commercializing zanidatamab ourselves. And I think the future financial returns that we will be entitled to based on the ultimate commercial success of zanidatamab with both Jazz and BeiGene, I think, kind of justifies that decision. And we're building this great portfolio behind zanidatamab of wholly-owned agents, which is now transitioning from preclinical into clinical studies. So excited about the commercial potential we still have with zanidatamab and excited to see where our agent ends up as our first approval as a company potentially this year as well as focusing on our own attention in development resources on this wholly-owned portfolio of antibody drug conjugates and multispecific antibodies.

Great. Maybe 1 other question on zani, and we'll go through the additional assets. In the BTC abstract recently, we saw some really encouraging data, specifically with response rate, overall survival rate, I think, objective response rate maintained at 41%. But the data is looking really strong. How is this data going to change how you're thinking about zani with a BTC strategy specifically? And how you're going to kind of position yourselves in the market?

Yes. I think the clinical data we've seen with our first pivotal readout in 2022 with Biliary Tract Cancer with zanidatamab and more recently with the update we gave at ASCO with a longer-term follow-up in the first median overall survival data point. just confirms to us what we had in mind when we engineered zanidatamab in the first place. So I think there were agents in the HER2 space, primarily in metastatic breast cancer between prior innovations made with Herceptin and Perjeta and Kadcyla. There were others who came along with other approaches, especially in the ADC format, and we designed something was very unique. It's the only bispecific antibody in late-stage development in the HER2-targeted space. And we designed it with a view that in certain tumor types in the HER2-targeted space, that the mechanism generated by zanidatamab might be more beneficial, especially in areas where there is heterogeneity in these tumor types. And I think in Biliary Tract Cancer, what we've seen with our latest data is what we expected from zanidatamab, a much higher degree of overall response rates than you might have seen with prior therapies. Very quick responses, as you saw on our BTC data earlier on the median time to response is less than 2 months. a durable, consistent and deep response in those who get a response to zanidatamab. And Biliary Tract Cancer, it's monotherapy only. And what we saw recently at the ASCO update is that these durable deep responses have tended to find a longer duration of treatment because zanidatamab is very tolerable. So you see very few discontinuations of drugs for tolerability reasons. And you've also seen this durable response turn into now a survival benefit. And we're hoping that with Biliary Tract Cancer, we can repeat that in our GEA studies. Obviously, we've done -- in our Phase II studies, you see the same thing a high-level response between 7, 8 out of 10 patients get a response to zanidatamab either interphase II with chemotherapy regimen or with a chemotherapy regimen in a PD-1. And you see the same deep consistent durable responses to patients of zanidatamab. And in our Phase II, you can see directionally that that's turning into a prolonged response, prolonged time on treatment and turning into something that directionally looks like a really encouraging survival response. Obviously, the purpose of the Phase III study, which we're running right now is to confirm in a 3-arm study between trastuzumab and chemotherapy as a control arm, what the benefit might be from zanidatamab chemotherapy regimen and a zanidatimab chemotherapy regimen, including PD-1. So I think what we're seeing in the clinical data set and we seen in BTC, we've seen in our early GEA studies, hopefully, we see it in our Horizon GEA-1 study that reads out this year. And we've seen it in our earlier studies, not only in metastic breast cancer, but other solid tumor types. We see the clinical data, which demonstrates the mechanism that we had in mind when we engineered this very original bispecific antibody that was trying to compete in a world of ADCs, as we talk about and it found a place in a particular tumor types, where that mechanism is well matched with the difficulties of treating these tumors. I'm hopeful in the wholly-owned portfolio that we have with these 5 agents moving into IND right now, that we're able to do that again. We've engineered some really interesting ADCs and multi-civic antibody structures, and we're hoping that the promise that we had in engineering them in a particular type of way, we'll see that in the clinical benefit that we see in these clinical studies, which we're starting to begin this year.

Great. And so obviously, a lot going on with zani, a lot going on beyond zani, and so maybe we'll switch there. We have your 5 x 5 R&D strategy. So maybe you can share with us a little bit high level, how the strategy came about? How do you really go about selecting targets?

Yes. So at the end of 2022 with the proceeds from the Jazz partnership and having the ability to allocate capital to the rest of the portfolio. But beyond zanidatamab, we set out to build a portfolio of 5 unique agents. And we did it with the view in mind that we're both accomplished developers on the antibody drug conjugate side, but also on the bispecific or now multi-specific antibody engineering side as well. One of our portfolio that showed our capabilities in R&D on both aspects of what we work on inside the company. So on the ADC portfolio, we decided we would pick a proprietary payload, which we have called 519, a very particular linker strategy and find 3 relevant targets that we thought would show the promise of our particular idea of how to design ADCs for the next generation. And so all 3 of those will be going to the clinic this year and next year. That gives us our own little portfolio of ADCs with different targets, very concentrated in gynecological lung and GI cancers intentionally. But I think some idea and there's still some diversity in that portfolio, but we like that idea of crafting a portfolio of ADCs as opposed to focusing just on 1, and we can prove a few things with the diversity between those 3. On the other side, we have 2 different ideas or formats in mind for how to improve T-cell engagers, which we worked on for a long time in my career and trying to find a way to make them more efficient and more durable as agents. And so we had 2 different formats in mind. One was a 2 plus 1 format to try and improve activity through binding by using 2 binding sites on the TAA and also with a low affinity CD3 as 1 format that we thought would improve T-cell engagers. And on the other side, the idea of doing a trispecific antibody where we build a CD28 co-stimulatory factor into the CD3 and the TAA. And we wanted to find a way to move at least 1 product from each of those ideas we had or concepts we had about improving T-cell engagers, efficiency and durability into clinical studies. So we came up with a strategy of 5 agents, which we think allowed us to explore our potential as both engineers of next-generation antibody drug conjugates and our thoughts on how to go beyond a traditional bispecific T-cell engager into something more. And we're really excited that we're on track now. We're actually a little ahead of schedule of putting all 5 of those agents in the clinical studies in the next 24 months. And then the clinical data will confirm to us, hopefully, that we've done a good job in how we thought about these agents, how we engineered them, how we build quality to every aspect of how we develop these up to clinical studies and then be able to understand what their potential could be in the marketplace against other potential agents in development and standard of care to really try and dramatically improve the standard of care for patients at the earliest line of therapy we can likely in combination with other agents and with the hope that survival benefit is everything. And so trying to improve that survival benefit for patients and indications we've selected, which have tended to have a bad prognosis. And therefore, some of the lowest overall survival rates on a 5-year basis when you look at data available in the United States. So excited about showing our potential in our new organization. Behind the 5 x 5, there's a rich substrate of additional agents that we could work on with more novelty, more diversity, more value, both on the ADC product modality, the T-cell engager product modality and a little bit beyond that. So I think the 5 x 5 for us is just a start. And I think beyond that, there's our ability to create additional agents which can move into the clinic at probably an R&D productivity rate of 2 new INDs per year annually from 2027 onwards. We've been working over the past 18 months as well on that portfolio and developing it, identifying the agents want to move forward and pushing them forward so we can meet those time frames.

Great. A lot going on. Maybe with 171, you touched on briefly. You've shown data kind of in these multiple configurations. Anything else you can share with us about how kind of the 2+1 was selected and how that decision was made?

Yes. And I think -- I know ADCs have gotten all the headlines in the last 2 years, probably because of transactions that might have occurred around those and additional approvals and ADCs. I think what we're finding now is that T-cell engagers as an approach, at least among KOLs is becoming something that's much more interesting because of some of these innovations that we're making to try and improve activity and improve tolerability at the same time. So we had this concept that we could use this idea of trivalency in an antibody and try and see how we could use those binding sites in a certain geometry to try and do that. And so we were looking for a target that would be really interesting to understand that this 2 plus 1 format, which means 2 of those points are going to be used to bind to the TA of interest and then a low video CD3 and a brand-new structure for us. So mesothelin has been a well-understood target for a long time frame. It's a very strong expression profile. It's a biomarker of interest in a wide range of indications not just in gynecological cancer and lung cancer, but also in the GI cancer, including pancreatic. So it's been a target of interest. It's been difficult to develop in a UC product format against mesothelin. Other approaches have been tried. There are some CAR-T development we felt, given the nature of the biology understood mesothelin and this issue of understanding there is low expression in normal tissue compared to tumor that you need to make sure that you can be very specific about high and medium expression levels at existing tumor to avoid this low expression that exists in normal tissue. So we felt this 2+1 format would be mesothelin will be an interesting target to try to prove our point, which is by having 2 binding points on mesothelin necessary to engage the CD3 is a way to differentiate and to get the T-cell activation engagement where you want it. And there are other approaches people are trying in tumor-activated mechanisms. We just thought this is a very simple but elegant process, so that it's required to bind to mesothelin to be able to engage CD3. And again, that doesn't happen in the low expression, it's targeted to happen in the medium-to-high expression. Therefore, there's hopefully some belief, at least preclinically that we can show that we'll get much more engagement in the tumor than in normal tissue and expression. And I think there's also an issue with mesothelin, whether it's a soluble mesothelin because of shedding, it has only 1 binding site. So therefore, the dual binding site avoids this issue of engaging the soluble mesothelin, which I think has caused some of these issues of folks trying a similar approach. So mesothelin is very -- has been a very intractable target. It's a very important target. It's meaningful in a broad number of indications. It might be perfectly suited to proving our concept of a 2+1 format T-cell engager providing a benefit, where other structures have not been able to. And we're excited to put that one in the clinic this year and understand in clinical studies, whether we confirm what we've seen in preclinical data, which shows more activity and a better tolerability profile.

Great. And on the ADCs, I think you've touched on this a little bit, but you're taking a different approach to what we've seen in -- before in the clinic using kind of a novel proprietary payload. Maybe can you talk to a little bit of the rationale on the approach there, the difference in design features and what it means for efficacy and tolerability.

Yes. I think the whole industry of ADC developers learned a lot from the [ DX DE ] portfolio that's been developed originally by [ DCS anko ] and then in conjunction with their 2 partners. And I think we watched that and we understood that. And we did a complete pivot on our concept of a next-generation ADC, and how they should be designed a couple of years ago. And the results that you're seeing now of these ADC is going in the clinic as a result of that. And again, we took the approach of going towards a modestly potent but proprietary TOPO1 payload. You think campus and analogs are really the payload of the day. But we think reducing the potency beyond what you might see with repurposed drugs like Exatecan was important. A very simple linker strategy that designs in a specific amount of instability into the linker to allow us a certain predictable amount of bystander killing effect was important. And then the one thing we added on our own, which we thought was another innovative step was because our we're protein engineers at heart. We think there are improvements that could be made on the antibody optimization characteristics that would be more effective in delivering an ADC payloads into tumors. And so we focused on that as a place that we could make a difference and be differentiated. So if you look at the antibodies that we've selected and optimized for all 3 of these ADCs, you'll find that they have properties not just related to binding to the specific target, but internalization and tumor penetration is really important to payload delivery, where you want it to the target tissue. So if you look at our folate receptor alpha ADC, for instance, which is the first one going into the clinic this year, ZW-191 and if you look at the data we put out at AACR in preclinical models, where we sequenced all the antibodies on other folate receptor alpha ADCs. You'll see that nothing internalized or penetrate tumors as well as the one we have on ZW191 in the models that we've tested head to head. So of internalization and tumor penetration is important to effect the payload delivery in an ADC structure. We think it is. Our clinical data will tell us that, then I think that innovation we've made and built into all 3 of our ADCs. So hopefully, if we're right about that, we'll be able to find a more effective delivery of payload and maybe pick up some additional activity and efficacy, but not at the cost of tolerability that you would see by doing other things with the payload and linker to try and generate activity there. So we focus on that for a couple of reasons. It's the one place we can make a difference that maybe others have not focused on. And we're well suited to do that in both mono binding and in the future in biparatopic and bispecific binding ADCs, but also we have this thought process of ADCs being effective combination agents. So really replacing chemo regimens, but working with standard of care, not as monotherapy. So the tolerability profile of ADCs needs to improve in order to move to an earlier line of patient care and to combine with standard of care. And that's where we think the place is that you can really make the biggest benefit for patients in the broadest population is by thinking about these as combination agents. So tolerability becomes a much more important factor, when you think about combination versus monotherapy. So we're really excited to understand if we've engineered that right, have that concept and philosophy, right? It's on all 3 of our ADCs with a similar payload and linker strategy, similar idea around optimizing antibody for characteristics specific for an ADC structure to drive activity. And ZW191 will be the first one. And then we've got 2 other ADCs going into clinical studies next year. ZW220 would start -- not be 2 ADC and ZW251, which is our GPC3-ADC for HCC.

Great. And you mentioned it a little bit, so ZW191, the folate receptor alpha program. Some of the preclinical data has seemed really promising in these low expressing tumors. Anything you can share more about how you're specifically thinking about how we would approach it in the marketplace with the program? And what kind of the real opportunity could be for our patients?

Yes. We're really excited about the preclinical differentiation we've seen in the models, and we've released some additional data at AACR recently, just around at least in preclinical models, we seem to have a range of activity and expression levels that's not been seen with other folate receptor alpha ADCs. And we've done used some of them as benchmarks. On the other side, if you look at the GLP nonhuman primate toxicology work that we did, which we summarized at AACR, you'll see that we're getting to levels of tolerability that's not really been seen in anything well that's been generated other than maybe the DXC portfolio, and we seem to be beyond that a little bit. So at least preclinically, we're seeing evidence of what we wanted to engineer these ADCs from both a breadth of activity at different expression levels of multiple tumor types and also with a tolerability profile that looks fantastic and beyond what we probably expected when we designed it. So for us, we need to find clinical settings in the folate receptor alpha-targeted space that will allow us to confirm this in clinical studies, but then also take advantage of the characteristics that we might have that differentiates us from other folks, who are developing other ADCs against the same target. So what we engineered this specifically to explore the breadth of potential of clinical settings for folate receptor alpha might be an important biomarker. So we'd like to explore that breath in multiple tumor types, and we'd like to be able to -- we design it to be able to work in different expression levels, not just in high or high medium, not just in a more isolated case of ovarian cancer or platinum-resistant ovarian cancer. But in the breadth of all the indications of folate receptor alpha is important, whether it's heterogeneity, whether it's different expression profiles and all these tumor types. We want to explore that in Phase I to understand it in a clinical setting, whether our human data and Phase I can confirm the promise that we see right now in the preclinical models we've done, which clearly differentiate us from the others who are developing similar forward receptor alpha ADCs, whether they're TOPO1 payloads or non-TOPO1 payloads. And obviously, we think this TOPO1 payload is the choice. That's why it's on all 3 of our ADCs. We're really excited about the Phase 1 confirming that aspect to us because we certainly see it in the preclinical data, we see to confirm that in a clinical setting.

Great. Maybe on ZW220, competition has actually seen some setbacks. And maybe could you talk about how you think ZW220 can be kind of differentiated relative to the competitive landscape?

Yes. So obviously, NaPi2b is a well-validated biological target is well understood. There have been 2 previous attempts from sponsors, first Genentech and then Mersana to try to develop ADCs against that target. It's a really interesting target, both in gynecological cancer and in lung cancer. So it's something that we were really interested in. I think we learned a lot from the 2 predecessors, who both developed ADCs, neither of which made it to market. And I think we learned a lot about them. Obviously, what we're developing in terms of payload, linker strategy and the antibody is quite different. So I think we've learned a lot from the other 2, the biology is better understood because of their efforts try to develop an approved ADC against that target, and we use that in how we design our own structure. And we're really excited about, again, the specific TOPO1 payload that we have on that ADC being our 519 proprietary payload. We're excited about the linker strategy we have. And I think we're really interested in the antibody structure that we have in that place -- or sorry, in place for that ADC. And we're hopeful that with the configuration we have on at ADC, we'll be able to find activity where the 2 previous agents did not and with a tolerability profile that is much better. And if you look at our preclinical models that we've been working on for ZW220, which is going to clinic next year, you'll see that our preclinical models will confirm a good tolerability profile activity, which is really interesting and compelling. We've decided to do that one in a DAR4 configuration as opposed to DAR8. We always develop both, and then we make a decision at the end is which one to take forward. So we decided to use DAR4 as opposed to DAR8 we follow receptor alpha might give us a little bit more tolerability and be able to dose up into an effective range. And we've also decided there to mute the FC on that antibody with folate receptor left at active. We think that will provide a little more activity. And I think in the NAPI2B,-ADC, we decided we would mute the FC and not bring in some other activity. That's one thing we learned from the predecessors who are working in this area that, that might be an important for this particular target and not folate receptor alpha. So we're really excited that this might be helpful to similar patient populations of folate receptor alpha, at least in gynecological and lung cancer. It is a different type of target. It's got a different expression profile. It will differentiate us a little bit from ZW191 because the DAR is different and how we deal with the FC is different, a little bit of diversity there in our choices. And again, quite excited about looking at that as a combination agent in combination of standard of care that might be appropriate either gynecological or in lung cancer.

Great. And maybe ZW251, so a novel approach here kind of using an ADC targeting GPC3, what can you say kind of in terms of how the approach was picked and what your kind of expectations are for the program?

Yes. On this one, we were looking again for the opportunity for a well understood target. Obviously, GPC3 is a very interesting target in HCC. Many developers are working on approaches against GBC3 because of the level of expression in these patients and it being just a strong target of interest. Most folks are doing it with other product modalities, being a lot of CAR-T, T-cell engagers. Now you're seeing radioligand therapy. Our approach was to try and find a way to have a chemo-like regimen be available for these patients. And obviously, chemotherapy is not indicated in this patient population just because of the nature of the liver and how crafty he is in dealing with that. So we know preclinically that it can be effective against HCC. We just haven't found a way to do this in patients. We think the concept of an ADC being a targeted smart chemo regimen might be something interesting in this patient population. And we still think the best benefit for patients can be in looking at a combination of standard of care. So standard of care right now is A+B with PD-1 and VEGF. The idea of giving the possibility of a smart chemo regimen to be used in combination with those agents in a very early line of therapy for this patient population would be significant to the potential survival benefit. And many of other therapies, which are being worked on against this target are really monotherapy approaches. They can't be combined as readily with other agents. So we think that's important. So we were looking for a target of interest that was a significant unmet need, we're providing a regimen that's not yet currently available, but doing an ADC format might be really interesting to study in this patient population. And so we're really excited to look at a completely different product modality. I guess a target that's quite busy with lots of other different types of approaches. But we think this might be the right approach for a combination strategy for this patient population. So really excited. It's obviously a more narrow set of indications than mesothelin or folate receptor alpha or NaPy, but it shares the trades of being a very strong expression profile, a very well-understood biological target. And really excited to get that one into clinical studies next year as well.

Great. So kind of a unique set in terms of internal capabilities in terms of ADCs, bispecifics, trispecifics, do you see it really an opportunity here to expand beyond oncology for Zymeworks?

Yes, it's really interesting. Like we have a tremendous amount of substrate in our group to develop even more innovative biologics for oncology on the ADC side. All these 3 ADCs are putting in clinical studies this year and next year are mono binding. We've done a lot of work around biparatopic bispecific binding ADCs, I think that's interesting. This is a single payload ADCs in the next 3. We have been working on dual payload strategies as well as the next-generation payload beyond [indiscernible] in analog. So our oncology portfolio is rich. But we have done work in the past using our platforms, especially our bispecific platform, in areas outside of oncology, including an autoimmune, inflammatory and dermatology. So we have had a history of working there. We have some opportunities to progress some programs that we think follow-on along some of the interest right now and looking at broader target coverage for some of these particular disease areas, where we've seen single-agent single-target therapies be very effective, but they do hit an efficacy wall, they do progress. And so there's a thought that a broader universe of target coverage in a single biologic that might get you into multiple pathways could be the way to break through that efficacy wall that we seem to be hitting in multiple patient populations in all of those areas. So we've been working in this area for a while. We haven't talked a lot about it. We've been trying to be focused on oncology, but we do have some assets which are differentiated, which are multispecific, which we think might have a place in this currently emerging theme of looking at multi-specific biologics structure to get broader target coverage, and so we're really interested in moving some of these programs forward towards the clinic and at some point, describing that to people as to what we have and what the strategy is with autoimmune that might be different than oncology and why those 2 things may fit together more obviously than you think. We have an R&D Day planned in Q4, and we'll probably wait until then to talk a little bit more about that strategy and by them will have -- help build a lot more progress in the rest of our business with zanidatamab and the first 2 agents going in clinical studies from a wholly-owned portfolio. It might be appropriate to describe not only what's next for us beyond the 5 x 5, but how that scope might get broader than oncology, and why that might be really important for patients and might work well within the Zymeworks structure.

Great. What about maybe a minute on partnership strategy? Any perspectives on how you think about partnerships with 5 x 5 assets?

Yes. I mean, having done this for 37 years, there's a lot of great medicines that we developed in biotech that we would not have been able to get to market in the breadth or the speed to patients that we would have liked without the partnership of pharmaceutical companies in our sector who tend to have greater resources sometimes, the ability to put more capital against opportunities and obviously have commercial infrastructure in place to get these medicines to patients, sometimes more quickly than we can in biotech. [Technical Difficulty] ambition is eventually to become a commercial company. And I understand that because you can end up getting increased profitability for the innovation that you make. I think partnerships are important for us. There are certainly important for zanidatamab we would not be progressing zanidatamab as quickly on our own as we can with Jazz and BeiGene as partners. And so I perspective as well. I would expect with all the things that we have available some patient populations. We will have to strike probably a series of partnerships to allow us to continue development, fund that development and commercialize. What's different now with zanidatamab with the 5x5 as we'd like to be a partner in that. So we would like to be a continued co-developer. We'd like to be a co-commercialization partner with those people, who want to join -- collaborate with us and move some of these agents forward. So I think you will see us look and evaluate a number of different partnership structures that allows us to move all of these great agents forward towards the market, but in a way that's different than we did before, which hopefully keeps more of that innovation value for our own shareholders. And I think, fortunately, in ADCs and then TV engagers and certainly in autoimmune as well, all those areas are in high demand from potential partners or unique differentiated assets certainly have a whole host of those, which gives us possibilities for different partners. I think we'll start to put that in place. I don't know if it's this year, but over the next couple of years, we'll put that partnership structure in place that allows us to move forward. but also keeps a good share of the value of the innovation that we're making inside our company for our own shareholders and be mindful of that.

Great. And maybe 1 last question, on cash runway. So you've guided to second half of 2027. What is that getting you through? Is that getting you through kind of the IND phase for all of the 5 x 5, or what can you share on the runway?

Yes. Fortunately, since we completed the Jazz deal in the end of 2022 and focused our capital on our wholly-owned portfolio, we haven't really had to worry much about our balance sheet, which is a nice position to be in. Fortunately, we've been very scientifically disciplined on what we work on invest in and also very financially disciplined about the cost structure in the company that we undertake and the obligation we take on. But we're still in a really good financial position. So we have a cash primary right now that runs out into the second half of 2027. So we don't talk a lot about balance sheet and cash runway in the company. We talk about disciplined financially, discipline scientifically. And then I think the cash runway will take care of itself. And we obviously have lots of optionality moving forward about how to replenish the balance sheet to continue to fund the great R&D organization we have that's emerging and accelerating.

Great. Well, thank you very much for the time. We really appreciate it. And I hope everyone enjoys the conference.

That's great. Thanks very much. Appreciate being here.