Zymeworks Inc. (ZYME) Earnings Call Transcript & Summary

Good morning, everyone. Good morning, everyone. Thanks for joining us for a session at the 42nd JPMorgan Healthcare Conference. I'm Brian Cheng, one of the senior biotech analyst here. I'm joined by my associate, Sean Kim, who is also in the audience. Up next, we have Zymeworks. We will be starting with a presentation by Ken Galbraith. Ken, the stage is yours.

That's great. Thank you very much. Thank you for opting to present today on Thursday at JPMorgan. Welcome, everyone. Thank you for attending. Just before I get started, I just want to reflect on a year ago being on this stage also on Thursday, right after 2 really important events in the company's history. One being the first pivotal study readout for zanidatamab in second line biliary tract cancer, which was in December, right before we came to the conference, which showed some very compelling data for zanidatamab and still the potential to be the first HER2-targeted therapy for that patient population, and that was a fantastic event. We also completed our transformative collaboration with Jazz Pharmaceuticals, who took on responsibility for the further development and commercialization of zanidatamab in conjunction with our partner, BeiGene and the APAC region. So both of those events were fantastic and give us a lot of momentum coming to the stage a year ago on Thursday. And I just wanted to talk a little bit about how we use that momentum from a year ago to really progress our strategy this year of broadening out our R&D portfolio beyond zanidatamab with our 5x5 strategy and how we did about that. And then maybe talk a little bit about what we think now is going to be a very exciting and newsworthy year for us in 2024. And hopefully, I can explain that to you. And you'll share enthusiasm at the end of the presentation, and then I'll be happy to answer any and all questions that you might have at the end. Forward-looking statements, please refer you to our SEC filings so I will try to make some forward-looking statements during the course of my presentation. So this is Zymeworks of today. We think we've really progressed our portfolio to really provide the opportunity for some unique and differentiated product pipeline, which is a combination of our focus on next-generation antibody drug conjugates and also our focus on multi-specific antibodies and a little bit of our future focus of how we might combine our medicinal chemistry capabilities, our antibody engineering skills to make even better multifunctional therapeutics and things like bispecific ADCs. I think with zanidatamab, we're very convinced by the data that we've seen to date on this molecule that has the potential to really transform the HER2-targeted therapy space in biliary tract cancer, where we've seen our pivotal trial readout and also in gastroesophageal adenocarcinoma, where we've seen some Phase II data that looks very interesting for us in compelling. And we're obviously in the course of a significant pivotal Phase III study -- global study, which we'll read out top line later in 2024 in conjunction with our partner, Jazz and Beijing. Beyond that, our partners, Jazz and BeiGene are evaluating some existing clinical data and potentially planning some potential indications for zani beyond BTC and GEA, and we're so excited to work with Jazz and BeiGene to really understand the full potential of that molecule as you move it through development and closer to commercialization. Beyond that, for us last year, it was about, again, broadening out our portfolio of ADCs and better bispecifics, which we think means drive specific. And we're really making good progress on the 5 INDs we'd hope to file over a 5-year period. We're about a year ahead of that. We've nominated 4 of those towards INDs that all occur in 2024 and 2025. And -- and the fifth one will be able to nominate this year. So I think folks will be able to understand exactly what those products are, what they look like, what the targets are, indication of interest and why we're excited about that, all going together in a very interesting portfolio. Beyond that, we've already started to think about what we do beyond the 5x5 approach of broadening out the portfolio, especially because we're about a year ahead of schedule, given the R&D productivity we've seen in our team. So we're starting to think about what the next generation platform looks like us to continue to create novel and differentiated antibody drug conjugates, trispecific T-cell engagers and maybe going a little bit beyond the current focus on oncology and to applying those platforms in autoimmune and inflammatory disease. And also trying to understand if we can do what we did before, which was go from being a bispecific engineering company to also incorporating ADCs through a strategic acquisition a number of years ago to give us the breadth we see today to see maybe we should be thinking about increasing that research scope even beyond ADCs and tri TCEs into other product formats. In addition to that, we've been very scientifically disciplined this year and the way that we've chosen these molecules and chosen to develop them, we've also been appropriately financially disciplined and ensuring that we can continue to support with a proper cash runway, all this exciting R&D that I'll try to explain to you in the course of the presentation. So we still have a cash runway forecast well into 2027 into the second half, which is fantastic. I think the combination of the near-term appeal of zanidatamab, this broad portfolio, creating the 5x5 second clinical studies and the longer-term R&D strategy to continue to innovate in these areas and potentially beyond, creates a very compelling opportunity for the company to be successful and hopefully a very compelling opportunity for investors who'd like to join us on that mission. So our approach starts with a focus specifically on the most difficult-to-treat cancers that we still have today. And this is a slide I brought into the company, probably the second day I was on the job to talk about where we want to focus our research interest. So we drew this big oval and looked at areas in oncology where we just haven't seen improvement in overall survival rates for too long because innovation has not been able to be brought to these patient populations. So as we start to fill in the 5x5 portfolio and also with our focus in Zymeworks with our partners, you'll see that we've started to clearly fill in products and opportunities that are just well suited against these difficult-to-treat cancers. Yes, they're complicated. Yes, others have not been able to progress them. We think we're in a very good position with the multifunctional therapeutics we have and the unique mechanisms we might have to address some of the missing innovation in these areas. So we intentionally push our technologies into these areas of high unmet need and very difficult-to-treat cancers, and we think that's appropriate. But that's our starting point strategy. Beyond that, I talked about 2024, I think it's going to be a very exciting and newsworthy event for zanidatamab, obviously, the 5x5 portfolio strategy with the first 2 agents that are going to the clinic. And also beyond that. We'll have a number of opportunities throughout the course of this year to show the exciting work we've been doing over the course of 2023 and continuing into 2024 around zanidatamab with our partners, the portfolio and even the longer-term strategy, which we'll do a little bit later this year in our biannual R&D day in the fourth quarter. Again, I talked about this, but I think it's really important, and we took this approach from the day I got here was it's great to practice innovative R&D in a broad portfolio way, but you need to be as financially disciplined as you are scientifically disciplined about decisions to be made. We were in a very strong financial position. We made that slightly stronger by doing a private placement at the end of the year with our largest shareholder. So we feel very comfortable with the cash runway we currently have to be able to support the R&D initiatives that I just described on the last slide and we'll continue in future slides. And I think we still have the potential to improve that cash runway and ensure that on a long-term basis, we could support all the R&D efforts that we have inside the company, either unencumbered as we have now or in conjunction with further partners and collaborators. So as I said, we started life as a bispecific company, we made a very strategic acquisition a number of years ago to embed medicinal chemistry and bioconjugation necessary to make antibody drug conjugates directly in the company. So give us the diversity of using different product formats on a particular indication and allow the integration of our protein engineering skills, bioconjugation, medicinal chemistry inside the company. We try and use that integration to advantage because we're one of the few small biotechs who is able to do that in hindsight, that looks like a pretty smart transaction we did in a number of years ago. We have great core companies in making ADCs. We do have our own philosophy that we talked a lot about last year. that's in the design of the 3 ADCs that we're putting into the clinic over '24 and '25 and some very key beliefs. We're tending to focus on validated targets either positively, like with Folate Receptor Alpha or even negatively where folks have not been successful. I think a good understanding of biology allows us to take a little bit more innovative route on some of the platform elements that we put in our ADCs, including our proprietary TOPO1i payload to made a very specific decision not to repurpose an existing molecule like exatecan in this class to put on ADCs. We took the approach of trying to create a proprietary payload that had characteristics that might be ideally suited for an antibody drug conjugate and potentially make it work better than a repurposed drug on the end of -- as a payload. So that was an important thing. We also really focus on trying to optimize the antibody properties and specifically internalization and tumor penetration that we believe the secret ADC is working well and tolerable in getting to those early lines of therapy is focusing on ensuring you get an appropriate protein dose. We don't think it's strength of payload. We don't think it's stability of linker. We think it is focused on making sure you get an appropriate dose of a protein, which is in the optimum range. So we'll talk a little bit more about that. So we have multiple ADCs going to the clinic, which use the same payload, same linker strategy, obviously, unique antibodies and slight variations to give us a little bit of diversity in the portfolio. Beyond that, you can see here, we started life in ADCs by working with Auristatin payloads. We've created one on our own in the HER2 space, where we made an ADC format out of our biparatopic antibody, zanidatamab, which we're testing in Phase II this year in conjunction with a checkpoint inhibitor in non-small cell lung cancer. We also made another Auristatin payload with the same payload which Exelixis is still continuing to work on development. The 3 you see above are really our next-generation payload, our proprietary TOPO exploring these 3 targets, which I'll talk about briefly here. So on Folate Receptor Alpha ADC, we're obviously really encouraged with an ADC being approved in the gynecological cancer population that gives a thought that ADCs can be worthwhile. We think TOPO payload has the chance to really innovate further and potentially improve upon the responses we've seen with the first candidate in the market, and that's what we intend to explore and we tend to explore it not only in gynecological cancers, but use our antibody engineering skills to see if we can make worthwhile effort at indications outside of gynecological cancer and also make a worthwhile effort about variable expression levels with this target. So that's our design. It's going to the clinic in 2024 shortly as a DAR 8 version. This is some data we've previously published on this. We think this is an excellent molecule. We believe in TOPO payload. We believe our engineering skills around the antibody makes this probably the best internalizing antibody to penetrate tumor tissue of any of the folate receptor ADCs that are under clinical development today. And we hope to go into the clinic and prove that with our data. Just to give you an indication of how we differentiate the space because it is getting crowded. As I mentioned before, we've not repurposed exatecan as a payload as many on the top of this graph have done. It is a fast approach. We think the proprietary nature of payload might build some characteristics that will help efficacy and also tolerability that's our goal. We're not the only ones doing that, but we think we have a very unique approach. And we have an approach on linker stability, which we talked about this year, which might be a little bit contrary in living with a little bit of design and stability in a linker, and we think that will help efficacy and also reduce some of the cytoxicity and tolerability associated with these. And again, we're really excited to get this in the clinic this year and start to generate some clinical data to hopefully prove the hypothesis that we've -- that I've just explained to you. Beyond that, we've got 2 more ADCs coming to clinic in 2025 with a very similar payload. In this case, NaPi2b, which has another target of interest for us in some similar patient populations as Folate Receptor Alpha in this case, also in ovarian cancer and non-small cell lung cancer. We've taken a little bit of a different approach here with the DAR, which is 4, so a little bit lighter in the DAR and we think that might be more appropriate for this target as opposed to Folate Receptor Alpha other than that same payload, same linker strategy, same fantastic protein engineering on the antibody, which we think will benefit efficacy in some way. Really excited to get this one in the clinic. This is also data we've we published before trying to explain preclinically what we see in internalization, what we see preclinically in some of the models we've done. And we're, again, really excited to get that in the clinic. We're a little bit differentiated here between prior attempts that have been made by these 2 folks on the top of the graph, which again, we're not TOPO payloads. We're not very high doses of protein. And again, we're a different linker strategy. So we think changing those elements might give us an opportunity to be successful in this target for this patient population where others have not been. So we're happy to try to put this in the clinic in 2025 and look at our clinical data to see if we were right about that hypothesis as well. Again, slightly different DAR, but again, very similar format for this ADC. Beyond that, we've got a very unique opportunity to look in HCC with a GPC3 target, which is a well understood biology and is being pursued by different product modalities, CAR-T, T cell engagers, recent radioligands, as you know, -- we believe we are taking an approach with an ADC is very unique. It might be quite different. We're not aware of any other ADC approach that's just close to the clinic against GPC3. So we're very interested in this. One of the key attributes we're trying to get from GPC3 is to move to the earliest line of therapy for patients here because we think that's the place to get the most patient benefit, which means ensuring have an ADC it's tolerable up to be combined as standard of care A plus B and others. So really focused on getting efficacy from this ADC, but getting it with a reasonable amount of tolerability as a cost of that efficacy, so we can work in the earlier lines of therapy in patients and in combination with standard of care. That's quite an exciting and quite a different target for an ADC product format to graft but again, validated biology with other product formats, which gives us some comfort about antibody delivery and some of the aspects of using ADC and that will be in the clinic next year as well. We have shown some data around this to try to get a better understanding of our focus around tolerability as much as efficacy, and we will describe more of this year in some scientific presentations. Again, we think there still are limited treatment options in HCC. We see very poor overall survival. We think trying to find something that can be moved in the earliest line is the way to make a difference there and not something that's a later line therapy for patients. So that's our focus. That's where you'll see us in the clinic as soon as we can working in that area. And we think the combination of the payload approach, the linker approach and the antibody we use and the tolerability profile will allow us to get there. Beyond that, we continue to work, as I said, on our Auristatin payload. [ Zani-zov ] in the HER2 space, and we look forward to presenting some of the Phase II data after we've enrolled this study, and this is going to be ongoing this year. We think it is a very different HER2 ADC than others. And we think specifically in the non-small cell lung cancer space in the HER2 over-expressing population in combination with a checkpoint inhibitor, where we know there are some synergies with Auristatin payloads. And PD-1, we think that's a really interesting opportunity. And currently, there's not an effect of HER2-targeted therapy in this space. And so it still is open for something like zani-zov to potentially show a patient benefit and be first line. Beyond that, we did, as I said, worked on another Auristatin payload the tissue factor ADC, which is currently under development with Exelixis, which brings us back to the beginning of the company. So we did start out life as a bispecific company. Talk a little bit about that. We started at the bottom of this table, which is making bispecific antibodies for others, and many of those are still in development, either clinically or preclinically as this one is with our partner, J&J. Then we created what we think is a really intriguing biparatopic bispecific antibody in zanidatamab, which as I mentioned, we've had a pivotal trial in BTC, and you've seen that data, and you'll see our Phase III GEA data. This year, provides a very unique mechanism in the HER2 space, unlike anything else that's been developed or commercialized before. And that unique mechanism seems to have a very good place in early lines of therapy in tumor types like biliary tract and GA, and our partners will explore other opportunities to see where that mechanism can make a difference where other agents have not been able to do so. So excited to see the progress we make with Jazz and BeiGene over the course of this year. We turned our attention then to making what we think is the next generation of bispecific, which is a trispecific using trivalent structures to understand how you can build in another mechanism into a bispecific and potentially push up that efficacy ceiling. We seem to have hit in solid tumors and also reduce the tolerability associated with traditional bispecifics. So we've been working on a number of different trispecific structures. One of those with our 2+1 format against mesothelin, we'll go in the clinic this year and another one, which is our true trispecific TCE, which incorporates a CD28 co-stimultation factor in with CD3 in the same structure will follow after that in the early part of 2026. So we allow -- ADC is a real focus right now. We think this area of making better bispecifics is something that can give an opportunity for some of these targets that maybe ADCs can't as well. Really pleased after a year with our partnership with Jazz, a fantastic partner. We've been very encouraged by their progress. I think they're very encouraged by what they continue to see from zani in terms of progress in clinical data. And every time I see their presentations, is one of their slides they get more encouraged with zanidatamab. So it's really great in our business to form a collaboration with someone who shares your enthusiasm is willing to invest behind a product in the same day that you would have done yourself just they have more resources to do that. So really excited to have an opportunity to enter the market first in biliary tract cancer and that submission is underway in the U.S. right now. And following that, looking for our Phase III data, which will come out later this year and understand what benefit that might be for patients in that first-line GEA opportunity. Beyond that, our partners have talked about being able to expand other opportunities with zanidatamab where it really might make a difference because of the unique mechanism behind that. I'm really excited to see the breadth of zanidatamab in the future. We made this agent. We made it with a very unique mechanism. We thought it had a place in the HER2-targeted space. And so far that's coming through. And we just want to see how important this medicine might be in the HER2-targeted therapy space in the years to come. Beyond that, as I said, our clinical data in biliary tract cancer was very compelling. And obviously, we're discussing that with the regulators right now. Really excited about our GEA study, which will come out this year. In terms of epidemiology of this disease in biliary tract cancer. Again, we're starting in a second-line patient population using zanidatamab as a monotherapy agent. There are no HER2-targeted therapies right now available, so we still could become first. And obviously, the confirmatory study that's underway is moving to an earlier line of patients in biliary tract cancer and combining with standard of care and just seeing and really improve upon these compelling response rates that we saw with monotherapy, and it's really interesting to think about what might be possible in combination and a better quality of patient in a first-line setting. So we're encouraged to get that confirmatory study underway and understand where the future might be for biliary tract cancer. Obviously, we've seen some improvement in this patient population with the involvement of checkpoint inhibitors with GemCis has moved a little bit forward, but we think we might be able to do better with a very specific HER2-targeted therapy for this patient population. So we'll see how we do there. Secondly, obviously, the Phase III study we have in GEA is a much larger patient population. Again, we're looking for a first-line patient opportunity because we think that's where the benefit will be the highest. This is done in combination with chemo and also done in combination with chemo and a PD-1, in this case, BeiGene, our partners, [ tisle ]. So really excited this is a larger patient population, a little bit earlier line of therapy, a global pivotal study readout. Right now, we've seen some advancement with the combination of a PD-1 inhibitor with tras and chemo, which was the standard of care, it just hasn't moved the needle as far as we think is possible for this patient population in terms of PFS and definitely not yet any overall survival benefit with that combination. So from our Phase II data, we're really intrigued with the idea of really making a fundamental difference in this patient population and the broadest part of the patient population. And hopefully, we can show a significant clinically meaningful benefit in both PFS and OS. Beyond zanidatamab, we're trying to use those protein engineering skills, as I said, to look at trivalent antibodies. In this case, our plus T cell engager against mesothelin. I think the 2 plus 1 is a variance way to think about more activity, brand-new CD3 antibody, which is low avidity which we think will hopefully see the improvement in cytokine release syndrome and other toxicities that we've seen with other 2 plus 1 product formats. Recently one at ESMO, which was really interesting for us because we have a very similar concept here. This will be in the clinic this year. We think it's very differentiated. It is a target that's been very difficult especially for antibody drug conjugates. It's a very important target. It has been difficult to solve. I think this 2+1 format with a different approach on the CD3 might be that breakthrough, and we hope to go into the clinic and be able to prove that with clinical data. Beyond that, it's a little bit of the design. Obviously, as a benchmark here. We use the [ Tritec ] from Harpoon, which is one of the earlier molecules. And we do see a very fundamental difference preclinically in how 171's mechanism works, I guess, targets of interest, but some very difficult-to-treat tumors. So we're hoping that this preclinical data can translate into the clinic -- into the breadth of indications that we like to study. Beyond that, we'll focus on our further developments on our trispecific antibody approach, which is this idea of building the co-stimulatory factor of CD28 into the CD3 T cell engager. But doing it in the same structure, so you can balance the CD28 and CD3 together and hoping that's more successful than we've seen in recent efforts where we try to do it separately in combination. We published a bunch of this data at AACR last year, just to get a better understanding of what we're trying to accomplish with this co-stimulatory factor. We haven't named a specific target to go into the clinic yet. Most of this data was done with claudin 18.2, primarily because there's a significant number of benchmarks of other product formats against this target. So it was easier to see where we might differentiate from an ADC, an antibody, a bispecific antibody or other approaches. But we've not yet named the TAA. The fifth of our ages in the 5x5 will be this TriTCE co-stimulatory factor just with an unnamed target, we'll name that target this year. Again, we think it's a different approach to trying to improve CD3 T cell engagers and hopefully, building it into the same structure will provide the benefits that are listed here compared to other competitors' approaches to the same problem. Beyond that, beyond the 5x5 I said we're about a year ahead of schedule in R&D productivity, which is a nice problem, but then you got to think about what you do next. We have a lot of other skills inside the company in protein engineering and ADCs we'd like to put to work either separately or together. So we'll lay more of this out in our R&D day at the end of this year. But I think we have the potential of productivity to create 2 novel medicines a year that can go into the clinic from 2027 onwards. There'll be next-generation ADCs. We're going to focus more on our protein engineering skills around bispecific, biparatopic ADCs a novel payload beyond TOPO 1 and even dual payloads. We've been doing a lot of this work over the last couple of years and excited to start talking about it this year. We'll also move more from solid tumors into potentially hem/onc again. With the technology, we'll further enhance our T cell engagers into other trispecific platforms as we go ahead. And we'll look to see how much progress we want to make in expanding our scope into other areas we had expertise, but we didn't pursue the last couple of years because we're so focused on ADCs and our multi-specific antibodies, -- really excited about what potential there remains in Zymeworks to create even more medicines that might be unique and meaningful beyond zanidatamab and beyond the ones which are going in the clinic in the 5x5. So in summary, I think really comfortable with the vision we have in the company, the mission we're on to really try and make a meaningful difference in the most difficult to treat cancers and maybe also some other serious diseases outside of oncology. We have this integrated R&D engine inside the company, which is a very compelling combination of our protein engineering skills, bioconjugation and medicinal chemistry, which can work separately or together in an integrated fashion to create some really interesting medicines going forward. I think we're very focused on 5x5. We're ahead of schedule, which is great. We're thinking about what's next, which is what we should do. And I think we're just trying to continue that success in R&D productivity. From a commercial perspective, we're very focused on clinically meaningful to patients, which really means earliest line of therapy, first-line opportunity the broadest patient population, we can potentially apply our medicines too. And again, a strong commercial focus on very happy to have partner zanidatamab with BeiGene and Jazz going forward. We'll look to other partners that might be able to help us, but in structures that allow us to retain U.S. commercial rights for ourselves to give us the ultimate opportunity of being a commercial entity at least in the U.S. for these medicines that are coming out of the 5x5 in advance. So hopefully, you can see them, it's the fourth day of JPMorgan. I'm still very enthusiastic and not tired yet. We just started the year. I think it's going to be a very newsworthy year for the company. We're very focused on execution and I can't wait to be back here a year from now, everyone start to think about on a Thursday talking about how we did. And if it all of you to come back on Thursday next year to see how we did against what I just outlined for you. So thank you. Happy to take any questions that you might have in the remaining time. So thank you for your time and attention on a Thursday.

Thanks, Ken. Let's start with the Q&A. For those who are you in the audience, if you have any questions, you can raise your hand, and we have runners on the floor. For those joining us virtually, you can submit questions on our conference portal. Ken, maybe let's focus on zani and then we can focus the latter part of our Q&A session on the pipeline work that you're doing internally. So start off for zani, can you talk about the $2 billion peak sales that Jazz guided, how do you view BTC and GEA's contribution individually from your vantage point?

Yes. I don't think that's a -- it's a good question. I just don't think it's something I can answer. I'd send you to Jazz, but they might probably say the same thing, which is they haven't given more guidance other than trying to show the significance of where we think the commercial opportunity is with zani. We share their excitement. We share that guidance they provided. We've always believed that zanidatamab in a crowded HER2-targeted therapy space could make a difference for patients in the areas where other agents or other product formats have not been able to. And the uniqueness of the mechanism of this biparatopic antibody just allows it to generate efficacy that we can't see with other product formats. And that's what we had in mind when we made it. So it's not just [indiscernible] a combination of anybody. There's something unique about what happens with HER2 expression with this antibody. And in some tumor types, that's a tremendous advantage. You can't give with other product formats. And in some, it provides a little bit more incremental efficacy and in some cases, not as relevant. So I think there are many opportunities even beyond biliary tract and GEA to be pursued with zanidatamab. We were in the position of having some really exciting Phase I data across a whole range of tumor types. But without a partner like Jazz, who has more resources than we do in human and capital to be able to explore those. We were unable to explore those and had to focus and have more narrower set of indications. We've rectified that with our Jazz partnership with BeiGene. It's a lesson we've learned. And I think in our portfolio, we do have some opportunities. Folate Receptor Alpha is one of them with our ADC where there's a breadth of indications there that if we can be successful in broadening with indications beyond a subset of ovarian cancer patients getting to multiple expression levels with that agent. I can see a situation where a partner might be able to allow us to go faster and broader to explore all those areas and not leave some of them behind a little bit too long. So I think there's lots of opportunities in that data set that's well laid out in Jazz's presentation of indicating where they might go next.

So maybe turning to your internal pipeline. There's lots to talk about there. And for 2024 for your R&D update, we definitely look forward to that. But there are a couple of updates that I find very interesting today. One is the 2 INDs per year goal starting from 2027 and also the autoimmune expansion strategy here, right? So maybe let's start off with more of a broad question. As you think about your ADC side of the story, there's also the trispecific approach. How are you thinking about the focus near-term? What do you think Zymeworks is going to be known for let's say, if we come back to the same table to talk about this in 2025.

Yes. I think it's not a goal to have 2 INDs years of goal. It's just what we're capable of. And I think when I came on board 2 years ago as CEO, we were a massive focus, if I can say that. We didn't have any focus -- we were trying to do too much in marketing anywhere. We have [ not done ] IND in 5 years, which is hard with a lot of smart scientists and a lot of great tools that I knew was there because I was on the Board for 7 years up until 2016. So we decided to focus in on just TOPO ADCs and our next trispecific platforms and try and see how productive it could be. And I asked the group to give me 1 IND a year over 5 years and something that's such a novel medicine we want to funded into the clinic. And they started giving me 2 and making it difficult not to do those because they are very novel and differentiated. And now we have the capabilities inside the company to put 2 additional medicines in the clinic every year from 2027 afterwards with increasing novelty, increasing diversity. There are some things in there that are -- we had we just didn't focus on the last 2 years. Coming back to, we have worked in autoimmune and inflammatory disease before. We have assets, we have programs, we have expertise. I just wanted us to be more focused. So I think some of these were going back to are things that will expand our scope that we already have. There are some opportunities that we see that maybe we could add a little something to us the way we did by buying an ADC company to get the medicinal chemistry and conjugation skills, some just growing organically from things we already have. So it's not an aspirational goal that we have. It's the capabilities of what I see in the R&D group to be able to produce. And so we feel obliged to move these novel medicines that fit our criteria into the clinic, and we're finding ways to make sure we can fund those appropriately with a strong balance sheet. We got proceeds from zanidatamab, which will come from BeiGene and Jazz. You have the opportunity to partner and collaborate with others. So I think we'll find a way to fund all the great medicines that are brought to me. And we're year ahead of schedule, which is a great problem. You've got to think about what's next, but it's just the productivity of the group is so much better. It's half the size. It focused down on fewer things in 2 separate groups ADCs and MSATs. It's amazing what you can do with productivity when you instill some focus scientifically. And we still have the financial discipline that we can afford to do it as long as we stay financially disciplined.

Any questions from the audience?

Just get over your first product in [indiscernible] biliary tract cancer or the other cancer are -- do you achieve versus your partner.

Yes. What's our share of the -- Yes. So obviously, we have an existing relationship with BeiGene and a new relationship with zanidatamab. The next stage for us is we are entitled to some milestones on approval by indication, by geography from both BeiGene and Jazz. We've guided those already contractually at least in global. So with Jazz, we have $525 million in approval milestones. So that's significant for us. And I think they're all based on approval. And then with BeiGene, we have similar, but they're somewhat smaller. On a commercial perspective, with Jazz and BeiGene, we're entitled to a royalty up to 20%, depending on how sales levels do. And we have $900 million of commercial milestones in our Jazz agreement paid to hit certain sales levels and also in BeiGene, a slightly lower amount given the size of the market. So zanidatamab was a great drug. We're relying on our partners to do further development and commercialization. It's a very important part of our financial strategy and our company when we think about how we build it and continue to have a very strong cash runway. We also think the value of future cash flows from zanidatamab that will flow to us contractually from Jazz and BeiGene remain well above our current market valuation. So we're hoping that disconnect goes away as we get more data, more approvals, launches underway -- that will get a more -- a more true reflection in our stock price of what we see as the risk-adjusted NPV of that. So that's about as much guidance I can do. I think -- it's a really great drug. And I think it's a great strategic fit for Jazz. And I know they're happier today about doing this deal than before because the drug continues to look better and better. From our perspective, we think from a commercial perspective, we do quite well -- from an approval perspective, as these indications prove, we do quite well financially, and it will be great to help us as we diversify our portfolio away from HER2-targeted therapy.