Good morning. Thanks for joining us for another session at the 43rd JPMorgan Healthcare Conference. I'm Brian Cheng. I'm one of the senior biotech analysts here at the firm. I'm joined by my associates, Sean Kim and Maryam Wagheie, who are also in the audience. On stage, we have the team from Zymeworks. I'll now pass the mic to their CEO, Kenneth Galbraith, for a short presentation, followed by a live audience Q&A. Kenneth, the stage is yours.
That's great. Thanks very much, Brian. And good morning, everyone. I'm not the entire team. I'm just one member of the team, but happy to be here today to present. I appreciate all of you sticking around for Thursday morning of JPM for me to be able to provide an update on Zymeworks. This is the three-year anniversary of my tenure starting as the Chair and CEO of Zymeworks. I've been really excited about the progress we've made over the past three years, but even more excited about the next three years for Zymeworks. I'd like to explain that to you. I think this is the third chance I've had to present Zymeworks at JPMorgan on a Thursday morning.
Really, every year we've been able to do this with making progress that's beyond the expectations that we've set and the guidance that we set at the beginning of each year. Fortunately for us, with increasing market capitalization every year, which probably reflects that progress. Obviously, over the course of next year, we would hope to meet or exceed the guidance that I'll talk about today and hopefully get enough credit for that to be back in that same position next year. I will intentionally make forward-looking statements today. I do refer you to our SEC filings that govern those forward-looking statements that I will be making during the course of my presentation. It is Thursday morning. I'll try and keep my presentation pretty short. It's a pretty skinny slide deck.
And then, happy to leave more time for questions or for you to wander off to the next presentation or meeting. So this is my third year at Zymeworks. But obviously, we've been making a tremendous amount of progress over the last 10 years in Zyme from the very early days of our original antibody engineering platform, Azymetric, where we started life as really making very interesting bispecific formats for partners, including people on the list, including Janssen, which is still prosecuting what I think is a really interesting one in clinical studies. Then we turned our attention to making something that we thought was very innovative for ourselves. And that's where zanidatamab came from, a very unique bispecific or biparatopic antibody, which we invented, developed.
Partners came along the way, BeiGene and Jazz Pharmaceuticals, to end up in a situation where we got our first FDA approval of our very first medicine last year, as you know, in second-line biliary tract cancer monotherapy in the U.S. And Jazz has now launched that in the U.S. market. So entirely proud of the trajectory that we've had. But we do continue to evolve our platforms, continue to innovate.
So lately, you've seen us now develop five ADCs and T-cell engagers of our own making in a solid tumor portfolio, which continues to be wholly owned, as well as most recently, as we laid out at our R&D day in December, now moving from even from best-in-class opportunities to things that are a little bit more novel, a little bit more diverse, and give us a chance to have both first-in-class and best-in-class opportunities, and also expand our horizons beyond solid tumors and looking at patient populations that are in need in both hem-onc and also in autoimmune with our first program announced in December at R&D day targeted for a 2026 IND. We do embrace the diversity of both being an ADC company and, I think, what is a great protein engineer, as we've proven with zanidatamab and some things we've made for partners.
So we like the ability of having options and product modalities to solve issues around targets or pairs of targets that we like. We're going to continue to look for opportunities to be diverse, but also continue to look for opportunities to meld those skills together that are both inside the company. So we will be looking at a lot more bispecific, biparatopic formats of ADCs in the future beyond what we were able to do in the first part of the five-by-five portfolio. So really excited about how far we've advanced in 10 years to get to our first FDA approval. And I think the future beyond this looks pretty interesting for us if we continue to innovate and evolve in an increasingly competitive environment, as you're aware. So I'd like to kind of explain where I think we're going with that over the next period of time.
We've been very fortunate to always work with the mentality of working with partners where we can to advance our new medicines more quickly, more broadly, with maybe more capital or more resources than we can. We started this early on with folks like GSK and Janssen, as I said, and more recently, it was extremely important for us to have strong partners like BeiGene and Jazz Pharmaceuticals to really get zanidatamab development finished, get onto the market, and still have a number of indications and opportunities to expand zanidatamab or Ziihera, as it's now known, into other indications and more globally, so we still do think about this strategic partnership advantage in being able to move faster, move more broadly, maybe have a broader portfolio than we can undertake on our own.
We're well-financed, but I think partners can bring something to us in drug development, which might be very important. We're very proud of the middle graph here, which is not a lot of biotechs get to the point of being able to say they've got an FDA-approved medicine that was internally developed and discovered by the same scientists who are still at Zymeworks working on the next innovation. So really proud of Ziihera. It is the only approved bispecific antibody in the HER2-targeted space initially for second-line biliary tract cancer, but obviously with a number of other registration studies ongoing, including a very significant phase three readout targeted for Q2 this year in first-line GEA, which is a very significant patient population globally.
We really have an opportunity based on our Phase 2 data to hopefully change the standard of care for a pretty broad patient population that's in need of an improved standard of care for that disease. We're really excited to have that table inside with the number one beside it. Our goal is we're not finished yet. The goal that we're striving for at Zymeworks is to turn that one in that middle table to two or maybe three in the future. That's the focus of what you see on the right-hand side of the slide with the wholly owned candidates. We now have six agents that are either in clinical studies or moving towards clinical studies, five in solid tumors, one in autoimmune disease, COPD. We think there's a really interesting innovative medicine. The preclinical packages supporting these are very high quality.
We're looking forward to seeing how we can translate those innovations into clinical studies and understand whether we can really get a benefit that's a unique mechanism, a differentiated clinical benefit, and maybe be able to move standard of care beyond what we see now from current standard of care or other emerging developments. That's what we do with zanidatamab. We know we can do it. We're looking forward to having the opportunity to do that again with both these six new medicines, but also with other agents that we continue to work on behind these. We get some comfort from knowing that we have a very strong financial position to prosecute the size of this portfolio. It is wholly owned.
And obviously, we do think clearly about how partners could join us on the route for some of these products and move us faster or broader. And we'll always look for opportunities where that may be beneficial for us to move these medicines because we do really believe in that strategy. And we have the opportunity to do this. It's nice that it's wholly owned right now. I think we have some really interesting medicines in areas of ADCs and T-cell engagers and this bispecific autoimmune program we have that are obviously things that are of interest right now to potential partners. Beyond that, this is our current product pipeline. It's a little busier than when it was just zanidatamab. So that's an evolution over the last three years. I won't have time today to go through the diversity of all the molecules that we've made.
It seems broad, but we still are very focused in solid tumors, really around gynecological cancers, GI, and thoracic. So I think we've tried to stay focused even within solid tumor. We are moving a little bit further afield into hem-onc and autoimmune, but again, in a very focused way and looking specifically at indications or diseases where we think our multifunctional therapeutic approach might be advantageous to move the needle on standard of care. So I think we can be a little bit broader, but still maintain the focus that we've done over the past few years, which has allowed us to really exceed expectations for what we set out three years ago. I think I talked about a five-by-five strategy of trying to have five new medicines in clinical trials over five years.
And we did that, and we should be able to do that in three and a half years now if you look at our current guidance. So I think we have been more productive. We have been more efficient. I think you need to be. We've had a lot of talk at this conference about enhanced competition on a global basis. I think that's really good for the sector. It's been really good for us. It's pushed us to be more innovative. It's pushed us to be more aggressive in timelines. I think we'll continue to do that. And I think that will leave us with a sector overall, which I think is more innovative, more aggressive in moving medicines to patients more quickly. So we really embrace additional competition no matter where it comes from around the globe.
I think it's going to push our sector to really be better overall. We're really attuned to doing that. I will focus most of my time today talking about our two clinical agents, which have moved into the clinic last year, ZW171, which is our mesothelin two-plus-one format T-cell engager, which is trivalent, not trispecific, but we'll talk about that, and also our first ADC with our proprietary 519 payload on it, ZW191, which is a target against folate receptor alpha in a DAR-8 version. We'll talk about those two things, but I would want to draw your attention to ZW220. I don't have a slide on it today, sorry, but we will give updates later. ZW220 is our next ADC in the clinic. Its target is NaPi2b. It's in a DAR-4 format with a very different Fc mutation around it.
We did make a very big presentation at the ENA meeting in Barcelona in October. That entire presentation is on our website. I really want you to pay attention to that if you could moving forward. That's our next thing in the clinic. I think the preclinical presentation we made in Barcelona was very fulsome and really presents an excellent opportunity to maybe address the same patient populations as we're targeting folate receptor in gynecological and non-small cell lung cancer, but with a different target, different expression profile, and also a different ADC. So we're really excited about 171, 191. Talked with us today. Don't have time to talk about 220, but that's going to the clinic next. We're on schedule for it.
And I encourage you to really take a look at that because I think that's going to be a really exciting molecule for us as we move into clinical studies. So with that being said, I'll talk about the two that I'm supposed to talk about today. So ZW171 was our first agent in the clinic. It's a very uniquely designed T-cell engager with a two-plus-one format to really, it's our approach to really try and find a way to improve T-cell engagement results in solid tumor applications. And so it's on target with the areas that we're interested in. It's a broadly expressed target mesothelin, gynecological, thoracic, digestive system. Those are our areas of focus. It utilizes a trivalent structure, which we think the next bispecific should always be a trivalent or trispecific approach to try and get more out of an agent.
This is our approach of using kind of a two-plus-one format with two binding arms of mesothelin, which are single-chain fragment variable arms and a low affinity CD3 approach. And this is our way of trying to get directed T-cell engagement on tumor as opposed to off tumor, although they're both on target with mesothelin. So it's our way of trying to really direct T-cell engagement where you would like it. Others have other approaches with conditional activation, tumor activation, masking approaches. We think using an antibody, and if you look on the left-hand side of the diagram, the schematic there, and there's more detail published, you'll see it's a very interesting geometry of how we've set up this trivalent approach.
Again, that's intentional because this approach really does drive, at least preclinically, amazing activity against the areas where we want to in mesothelin-expressing tumors, but seems to really dampen down. We get great tolerability out of this agent. Great. We were able to use a different methodology to move into phase one with QSP from an FDA perspective to get a much higher starting dose than you might expect normal T-cell engagers to get because the tolerability profile was really, really amazing in preclinical development. Really excited about using our protein engineering skills here to really drive a next-level bispecific mesothelin as a target we chose because it is broadly expressed. It's on our target areas. We could also use this two-plus-one format in the way that we do it against other targets in the future.
We're really excited to see what we can do here. Obviously, mesothelin has been a target of interest for more than 10 years. Other approaches have not really been able to get enough activity in a tolerable range, especially with ADCs. We think this might be uniquely engineered to be able to use mesothelin as an important target in some pretty big indications, not only ovarian cancer, but lung cancer, and also for us, digestive system cancers, which is more of the focus of our solid tumor portfolio going forward beyond the five-by-five. We've moved this into clinical studies. We've done this with a very broad global footprint. We have maybe a more unusual number of phase one sites than you'd expect you would need for a dose escalation study.
I think as we've learned from others, if you would like to go fast in clinical development, putting a big global footprint down early just allows you to follow your data if it's positive in a much more aggressive and timely manner. So in this case, we're up and running in the U.S., several European countries, and South Korea. It's a very traditional dose escalation process to start at first in a three-plus-three format. This is being done in unselected patients. So these patients will be mesothelin positive or negative. It's a broadly expressed target. So majority of the patients will be positive. We won't select them on dose escalation. We will do that afterwards, obviously, when we think about backfill cohorts and moving to dose escalation. This program was translated from preclinical to clinical pretty quickly last year. Phase 1's up and running in a really broad footprint.
And I think there's a broad available number of patients for us to move this quite quickly. We did talk at R&D day about possibly having data to share on this initially during 2025. That still is the guidance that we have. It will be in a peer-reviewed medical meeting, not by press release and company event, because we do believe, I know others have done differently. We do believe that's the way you should present progress in clinical development is in front of KOLs and investigators in the medical community. So we will look for the opportunity to do that in 2025, provided we continue to progress the way we are and provided we have data that we think is meaningful enough to present in front of a medical community. And that's kind of our benchmark.
We're really excited about the opportunity to see what data comes out of ZW191. And again, it's a very broad phase 1 footprint. We should be able to find the right diversity of patients and expression profiles and tumor types. In this case, we're only recruiting patients with ovarian and non-small cell cancer malignancies. We've not included endometrial or pancreatic in this yet, but you can see they are on the chart here for expansion cohorts. ZW191 was our first ADC with our proprietary 519 payload, which we talked and published about before.
It's our approach to trying to find a more modestly potent camptothecin analog payload, which is proprietary to us, which we hope has the right potency range and also the right drug-like properties in an ADC format to go along with our thoughts about linker stability and to go along with our thoughts about what I think we've done as an innovation in these three ADCs going into the clinic, which is really focused on internalization and tumor penetration properties of the antibodies that we design. So we optimize antibodies to try and improve the performance of ADCs. And this might be something we do more than others because we're able to with our protein engineering expertise, but we think it's very important to get more effective payload delivery at the target site. And so this is the first one where we'll see evidence of whether that approach was correct.
Hope it is, because we've got ZW191 coming along with very similar philosophies, similar payloads, different targets, different patient populations, maybe different DARs, but this is quite an interesting approach for us. It's quite different from what others are doing. This is obviously a target of interest, been validated with a non-topo payload by mirvetuximab, which is on the market for gynecological cancer. That's exciting. We think we have the opportunity to go beyond ovarian cancer to look at other folate receptor alpha-expressing targets, and so that was the design of the antibody that hopefully will allow us to do that. With a modestly potent payload, we think that approach may be really interesting in some of these opportunities outside, not just in monotherapy, but potentially in combination.
So again, we've started this again with a very high starting dose because the tolerability profile of this agent was beyond, I think, what's been seen with ADCs to date. So tolerability in non-human primates and GLP-tox was 60 milligrams per kilogram. That's well beyond what we've seen with ADCs without giving up activity in our preclinical models. So starting at a, obviously, having a high starting dose allows us to get into an active range much more quickly as we expect to do with ZW171. Again, this is a pretty broad footprint for a phase one dose escalation study. You can see that there's a large number of countries in Asia-Pacific which are up and running as clinical sites. We think they're excellent quality investigators.
They have a broad group of patients with very diverse characteristics and tumor target in tissues that we want to target and also expression profiles. Initially, we're focused on ovarian, endometrial, and non-small cell lung cancer. There are obviously other folate receptor alpha-expressing tumors that we could go to. So again, this is up and running quite quickly. We're very hopeful, again, as I said with 171, to be in a position to provide some initial clinical data on this during the course of 2025 at a major medical meeting in a peer review format where the timing lines up and we have data that's meaningful to talk about. But really happy now with the way we've translated these first two programs from preclinical to clinical. We have three more coming in our solid tumor portfolio and one in autoimmune.
I hope that our team can keep up the speed and quality of the execution we've had over the past year, and I'm sure they can. For us, we're still investing in the future beyond the six compounds that are in the hem-onc pipeline. We talked about this at R&D Day. We have thoughts of trying to continue to be more novel, more diverse with mechanisms, structures, targets. As we move forward, we talk about it as advancing the portfolio even further, advancing novelty, advancing diversity. We call this our advanced portfolio. It's distinct just because we have the ability to drive more novelty into the next stage of our innovation wave in Zymeworks. We think we have some skill sets and platforms inside the company that we didn't utilize in the first six programs, which we can still come back to.
So bispecific, biparatopic ADCs, dual payloads. We have a novel payload that goes beyond the camptothecin analog class that we're really excited about. On the T-cell engager side, we have a lot more we can provide. We do have lots of masking and conditional platforms. We didn't choose to use them in the first two T-cell engagers, but we can. And obviously, we have good protein engineering skills to look at the ability to use a trispecific, trivalent structure in different ways, including dual targeting TCEs. So we're really excited about working on behind these first six programs. And also, I think our autoimmune program just reminded people that we do have good cytokine engineering skills as well, which we did in a more traditional bispecific format for COPD with our IL-4 receptor, IL-33 program. But I think we have a breadth of opportunities behind the first six programs.
Looking forward to that, and we think some of those programs could have applicability in multifunctional opportunities within hem-onc autoimmune inflammatory disease. Other ones, solid tumors, will continue to work there, but more likely in GI tract and maybe opportunistically in thoracic, so what does that mean for the next year or more for Zymeworks? As I said, really proud of what we've been able to accomplish as a team at Zymeworks over the past three years, moving our first medicine to FDA approval, which is an exciting point for biotech, putting ourself in a strong financial position, identifying an initial portfolio of six wholly owned agents, which we're prosecuting really quickly, and I think they're all of high quality right now, but we have optionality on which ones to take forward, how many, how partners might help us with that.
We're really excited about the position we put ourselves in in the past three years. After three years, we're getting a little bit of credit for it from Wall Street, although we still consider ourselves to be very undervalued compared to the prospects that we see ahead of ourselves. We obviously have a significant phase three readout in Q2 and first line GA with our partners, Jazz and BeiGene. We're excited about that. Both our partners, Jazz and BeiGene, are investing in a very significant way in clinical development behind the initial application. We're pleased with what those partnerships have brought to the ability to get Ziihera to a broader patient population globally and a broader patient population with multiple indications, which is great. We're on track, as I said, with ZW220 to go in the clinic this half of this year.
Pay attention to it as I tried to foreshadow. And I think beyond that, the GPC3 ADC that's coming later this year is much more alone in trying to bring ADCs into HCC or liver cancer. But we really think that's an interesting approach.
In 2026, we've got our final of the five-by-five solid tumor portfolio and our DLL3 tri TCE, which we think is just a way to be a little different than the wave of ADC approaches against that same target, as well as our first foray into autoimmune, which we're really excited about the ability of our IL-4, IL-33 to really maybe structurally and through the engineering get to a broader group of patients in COPD in a more significant way than we've seen with Dupi, which is approved this year in COPD, and that we may see with some of the IL-33 antibodies on their own, which are phase three data is due later this year for at least one of those. Incredibly excited about the next three years for Zymeworks compared to the even excitement of the past three years.
Guaranteed, the team at Zymeworks is very committed over the course of the next year, giving clear guidance on what we want to achieve this year. I think we've done that including R&D day, trying to meet or exceed all of that guidance wherever we can through the hard work and collaboration we have. Hopefully coming back next year on Thursday morning or earlier in the week to give you an update on what we've done and hopefully being able to progress the company that way gives us a chance also to provide some shareholder value, not long term, but even on a short term basis as we've done the past three years. Happy to answer any questions you might have. Thank you for your attention on Thursday morning to the presentation.
Thank you, Kenneth. Thanks for the presentation. We're going to switch over to Q&A.
Kenneth, do you want to join me here?
Sure. I'll stand.
Oh, actually, yeah, yeah, you can present.
I answer better when I'm standing. I don't know why that is, well, hopefully I do. You can judge, but.
I guess for those who are in the audience, if you have any questions, you can raise your hand, and we do have a runner on the floor, and for those joining us virtually, you can submit questions on a conference portal. Kenneth, over the last year or two, actually, yeah, over the last two years, we've been seeing Zymeworks doing a lot of strategic moves. Now you're at a place where your five-by-five is very real, and I guess just kind of more of a broad stroke, what really made it work? I think what's interesting to me is that I think last time in December, you hosted an R&D day. I think we touched on that a little bit, but just how are you organizing your R&D internally to make it efficient, and you're not just working on one modality, which is very distinct from other biotech company.
So how are you optimizing your internal R&D franchise to make sure that the products are rolling out in the exact time frame that you have laid out today?
Yeah, no, good question. Obviously, from what I presented, we're progressing really well on the quality of the preclinical assets we have and transitioning those to the clinic. I'm never quite sure what we've done right to make that happen, but we tend to have a strong focus inside the company, so clarity of what we're trying to do is in every single employee in the company. I think we did try to focus ourselves in solid tumors around those three areas, gynecological cancers, thoracic, and GI. We made a really great bispecific antibody for Janssen and prostate with the KLK2 CD3 that's progressing, but we're not working on prostate cancer right now, so try to be focused. Within there, I think we didn't try to take on too much. We said, let's put five new medicines in the clinic to get initial portfolio. There's three ADCs.
We did make it easier for ourselves by same payload. Those are all monobinding antibodies and ADCs. We didn't go to biparatopic or bispecific. We think they're all interesting and unique, but we didn't try to take on too much. On the T-cell engager side, we took two approaches. One a trivalent, one a trispecific, which I think tested our skills, but we didn't take on a dual targeting TCE or all at the same time. So I think having five was appropriate. And then we just built a team who could kind of make sure that we could handle that. So our clinical development team, which is not just in North America, but also in Singapore and Dublin, can execute those five programs in early clinical studies with the team we built.
And they can do it in a very efficient way with an outsourced component to that in a global manner because we have people in Singapore and Dublin who can complement the folks who got in the US. So I think we built the team necessary to execute that. I think that's good. So not taking on too much. There were things we were working on when I got here. We stopped. We had a CD47 preclinical program, which just decided we shouldn't work on. And so we did take away some of that. So it allowed us to focus on the solid tumor programs, but at the same time, we left enough room on our desk to work on autoimmune, which I think we might have talked a little bit about last year, and now you can see where we're going with that.
I think we have found a way so far to balance focus, but have a broad enough portfolio. We can decide how partnering works with that. There'll obviously be attrition. Not everything we've done can be best in class. We think we're really great inside the company, but 100% hit rate from preclinical to approval just doesn't seem to be possible in our business. So there will be some of that. So let's just manage that portfolio. If you only have one product in a biotech company, it's hard to decide that that's not best in class and we shouldn't work on it. So I think we've been able to balance moving the clinical portfolio away. I've just been really impressed with how we've moved the preclinical portfolio forward even more. So we really advanced a lot of the things that you didn't see here.
And that's probably due to Paul Moore, who joined the company in 2022 with me, who's got a long track record in ADCs and T-cell engagers and dual checkpoint inhibitors, et cetera. And I think he's brought a really collaborative approach to the research group. And that research group that's been here for 10 years is still here. So longevity of that core research group has meant a lot because they're a team. They've worked together. They can go quickly. And I think we've just motivated them with external pressures. I mean, you have to go quickly in this business, and that's only going to increase because competition's coming from all over the world. It's just not one country. It's everywhere. And I think that's just driving us to be better. So I think we're getting better at picking the best ideas.
We're much faster from idea to IND right now, and so far, we're pretty quick from IND to phase 1 data. I hope we keep doing that, so I think whatever we've been doing inside the company, culture-wise, teamwork, the type of people we brought on board, the collaborative nature of it, the global footprint we have, which is a little unusual for a small biotech, I think has just been able to keep that going much more quickly in a high-quality way. Hopefully, I don't mess that up by doing something different, but we do also need to change as we move along and progress, but can't complain about the results that we have so far in the quality and speed at which we've been developing these molecules.
Looking ahead into later this year, one of the major catalysts that you have is the GEA readout. It's a partner asset. So I understand that your commentary could be a little bit more on the limited side, but you have been developing this Zymeworks for some time. So I'm just curious, how do you frame what you want to see in this upcoming top line? How should we think about what a win scenario is? Because there's a bit of nuance in PD-1 negative, PD-1 positive patients. I don't know if you can kind of provide some commentary around just what to look for to the extent that you can.
Yeah, for Zymeworks itself, I mean, now that I'm standing here after the third year, this is an approved medicine in the U.S. We have an upcoming phase three readout that's not that far away. So we left all the commentary on that to Jazz. And fortunately, they presented earlier at your conference. Fortunately, you cover them with another research analyst. So I think I'll just leave the commentary for them. We clearly believe in Zymeworks. And I think in the course of our history of looking at that as monotherapy or combination, all the tumor types that we've looked at, we continue to see that Zymeworks because of its unique mechanism seems to outperform trastuzumab or trastuzumab and pertuzumab in combination. I think it's been true in all the data sets, whether it's something that was done early on.
Obviously, we're approved as monotherapy right now in second-line biliary tract cancer, but we seem to be able to generate results there from the single-arm study that we did that was the basis for accelerated approval that just outperformed agents which have been tried before in those indications, so we would hope that in this large randomized global clinical study in GEA, that zanidatamab would outperform the standard of care, which is still trastuzumab as a HER2 agent with or without a PD-1, depending on if the patient, but that's interesting for the patient to have on top of that. We would hope that zanidatamab would outperform trastuzumab as it has done in the history of our clinical development. By how much in PFS and OS eventually, that's not for me to talk about here.
Obviously, we think highly of Zymeworks, obviously Jazz and BeiGene too as well because they did join us in this effort and have been investing behind Zymeworks in this current indication for the indication coming out, but all future indications. But I think I'll leave the commentary to whatever Jazz said at their presentation this year. I wasn't there. Or you're welcome to follow up with them directly if you'd like to do that.
Maybe just going back to your five-by-five portfolio, phase 1 design for 171, 191, there's a lot of components that are somewhat in parallel. Can you just, I guess, two-part question, right? One is when you think about the dose escalation, where does that dose range land? Do you think that you could potentially see therapeutic efficacy early on in the dose escalation? And I think also second part of that is that when you look at your trial design, there's a dose optimization period, which is anchored on specifically ovarian cancer. Just curious, why that indication that you would want to just optimize the dose?
No, good question. Yeah, I think with both those programs, 171, 191, we did have the advantage. The tolerability profiles for both those agents are beyond what you've probably seen with ADCs and T-cell engagers before without giving up activity in our preclinical models. So that allowed us to have a much higher starting dose for regulatory purposes than you might expect. So it does allow you to get into an active range pretty quickly. We haven't announced those starting doses. We hope to do trial and progress posters this year at a major medical meeting. And you'll probably see the starting doses on those posters.
And so you'll get a sense of why we're excited about it. It doesn't take many cohorts to get something that we would expect to see activity, and we hope to see activity, and we hope to be able to see the same tolerability in our preclinical models in the clinic. So that's really interesting. We tried to straighten out the path for both of those dose escalations by restricting the types of patients we would take. And it's not all folate receptor alpha-expressing tumors. It's not all mesothelin-expressing tumors. We've picked a few patient populations who I think will give us better clarity of data and activity. So that's important. It doesn't mean that pancreatic cancer won't be an important element for mesothelin targeting. We just didn't do that in the dose escalation because that makes it more complicated.
I think it's important for us to optimize dose while you expand as well. We put down some dose expansion cohorts, which we disclosed here today. Obviously, data and the competitive landscape lets you revisit those through protocol amendment before you start the dose expansion, so you may find the data that comes out of the study or the competitive landscape just makes us want to think about how to do that. It's important that we think we try to optimize in one expansion cohort in a randomized fashion and hope you don't have to do it in all of the tumor targets, and we think that's the way to do that. You need to do that in phase one before you move forward. You have to have clarity and keep at it.
Moving forward into phase two or three without a clear dose, we just think delays development, delays the drug getting to patient. There's no reason to try to do that. So you might find that changes a little bit. I think ovarian cancer itself, especially with an ADC with a folate receptor alpha-expressing agent that's already on the market with mirvetuximab, we still have the same approach. We want to be the best performing ADC for that patient population. And I think we hope our phase one data shows that. But being the second or third ADC that might be used in sequence for a patient population, regardless of payload, doesn't matter if it's topo or non-topo, is just not the way to really make a difference for patients. And so it's usually not as great of a commercial opportunity.
I think if you look at Zymeworks in HER2, I think we have the opportunity to be first line in BTC, and that's the subject of confirmatory study right now. I think we have a first line GEA study coming out now that I hope is better than what is the existing standard of care, and so that's a chance there. I think for metastatic breast cancer, obviously, Jazz is running a study of looking at using zanidatamab after anti-HER2 progression. So maybe that's a chance to be second, but with a different modality, and maybe that makes sense. But we're very focused on being the best ADC in a patient population of anybody and moving to standard of care. Same thing with mesothelin.
We have to be a T-cell engager that can really move the needle beyond other approaches that are T-cell engagement plus move the standard of care. So that data will decide maybe where we think we want to develop it. And I think with Zymeworks, we were very aware of that. And that's why you see a lot more emphasis in BTC and GEA initially because the heterogeneity of HER2 expression there lent itself well to the way that Zymeworks mechanism works. So I think the early data allowed us to really figure out the right positioning of where that might make sense to do in clinical development.
So those dose expansion cohort strategies might change as we move into that with a protocol amendment, and you might see that, as well as combination cohorts, which we didn't list in the initial protocol, but intend to look at combinations as well. So you might see that as we advance this in dose escalation, that we'll have some more to say about the dose expansion cohort strategy, where we're going to optimize and what combination cohorts might make sense once you've optimized dose and monotherapy.
I think just to kind of.
You didn't like my answer. Okay.
No, no, no, no, no. I think you made an interesting comment about your past experience with Zymeworks, the distribution of expression and what you learned there. And I've been following, I follow this company called ImmunoGen. And it's interesting there because your 191 is more also of expression. You have to think a lot about just where to target, right? Because right now there's a commercial product more anchored towards the higher end of the expression spectrum. So I mean, realistically, just how do you think about, at this current time, I know that you don't have any clinical data on hand, but how do we think about, how should we think about where you stand?
Because you laid out the fact that you want to be best in class, but there is certainly already a commercial product that's tapping toward the more polar side of the spectrum. So how do you think about that folate receptor alpha market for 191?
Yeah, I think if you look at ovarian itself, I mean, mirvetuximab was a great breakthrough, the first ADC in gynecological cancer, great. There's obviously another phase three study going on with a different target, CDH6, from some competitors, which initial data looks interesting. Fortunately, that's ovarian expression only. But I think in ovarian cancer, which is an interesting market, but it might be well served with others, then we would have to think about how we beat those. I think if you talk to gynecological physicians, you'll find that endometrial cancer is still problematic in their practice and growing rapidly for some reason without an ADC or without a breakthrough in innovation. And obviously, we're enrolling endometrial cancer patients in our phase one. And wouldn't it be great if somebody else could be the first ADC in that indication versus ovarian cancer patients?
And also, non-small cell lung cancer, I think, is a renewed opportunity for novel ADCs because I think, as we've seen with the phase three data from several TROP2 ADC competitors, I think physicians have been disappointed with the lack of survival benefit, the lack of being able to identify or select patients that might benefit. And I think they are looking, as we've heard from them, for other targets where an ADC approach might drive a survival benefit in the long run or be able to select or identify patients at a time that would be perfectly suited for a topo payload. So I think those opportunities are available for us in folate receptor alpha. And obviously, those are very large commercial opportunities, if not bigger than ovarian cancer, especially ovarian cancer with a current standard of care approved and maybe another one coming along.
So I think we think about the competitive landscape, think about our data, think we have an ability with our broad expression profile to be in multiple tumor types. Hopefully, that's the case in our phase one data. If it is, I think we'll think seriously about the next stage of clinical development. We'd love to have the ability to improve upon mirvetuximab or to beat the next competitor coming along, either with monotherapy or combo therapy. So we won't give up on that until maybe it's obvious we're not going to beat them. But if not, there are really great opportunities for us to have a great ADC in patient populations that maybe need them and aren't as well served in ovarian cancer. So I think that's an important part of what we need to do with 191. 171 is the same. It's broadly expressed. NaPi as well.
So we just need to make sure that you match data mechanism with the right patient population with the right commercial opportunity. And that's what we're going to need to do this year, maybe starting this year with some initial data and definitely next year with much more significant data in more than two of those agents.
Great. I think that's all the time we have, and Kenneth, thank you so much for your time today.
That's great. Thanks, Brian. Thank you.