Hi, everyone. Welcome to today. My name is Phoebe Tan. I am an associate on Akash Tewari's team. Today I have the pleasure of hosting Zymeworks. We have Scott Platshon here with the Chief Business Officer. I'll pass it over for any intro remarks. Perfect. Thanks for having us, really appreciate it. Since I'm about two months into this role as the Chief Business Officer, I thought I'd just start with a quick introduction to myself, then give just a quick overview of the company. I'm the newly appointed Chief Business Officer for the past two months, but have been around the company for a long time. I joined the company from one of the large shareholders, EcoR1, where I spent the last 11 years. The reason that I often get the question of why join Zymeworks, it's really an amazing R&D innovation company. Some of the world-leading protein engineering and computation with an amazing group of individuals that have developed some amazing drugs that are in our partners' hands now in Vancouver. The company's at a really interesting and privileged point right now that has developed zanidatamab with our partners, Jazz and BeiGene, and we're really proud of some of the data that came out, and we can talk about some of the recent data from ASCO, and a deep pipeline behind that, some of which is wholly owned and some of which is in our great partners' hands. We really have two businesses right now, this highly innovative, large molecule R&D shop, which is pushing forward a really interesting and exciting oncology and immunology wholly owned portfolio, and an external innovation shop, which is really managing this portfolio of partnered economics and is looking to acquire additional economics. We're really privileged. The company's in a great financial shape with a robust balance sheet and is pushing forward a really interesting pipeline that we'll get into today. Awesome. Thank you. Just starting with Ziihera, the paper came out recently. There's some subgroup analysis that we've been getting questions about. I just wanted to start off with, if you have a sense of why we're seeing that patients with PD-L1 negative status are doing maybe better than those who are PD-L1 positive. Yeah. Thanks for the question, give me an opportunity to talk about my favorite topic. We're really proud of the paper and the work that's gone into Ziihera. Just to back up before we get into some of the subgroup analysis you're mentioning from the recent New England and ASCO presentation, I think the high level takeaway is zanidatamab is the standard of care in frontline gastric for all patients. You can see from the high level that it drove a meaningful benefit, meaning both on the triplet and the doublet PFS, and at the first interim, driving an overall statistically significant survival benefit in the triplet arm. I think what you're mentioning is based upon some of the recent subgroup analysis from ASCO and mentioned in the New England, the outcomes by PD-L1 status. As we know, a few years prior to our top line results, Merck put out their KEYNOTE-811 results, which showed only a benefit in the PD-L1 positive. It really makes sense that Zani is going to drive a benefit across both subgroups, as we're innovating on the HER2 side of it rather than a PD-1 side. I think the important takeaway and what was a resounding sort of feedback from the physicians that we've had the chance to talk to, both at ASCO GI and pr obably even more consistent feedback from the ASCO meeting, is that regardless of PD-L1 status, we would expect strong uptake. There is some interesting biology that we can get into of zani. Zani does drive PD-L1 upregulation, and so there's a lot of interesting theories about that may be driving some of the benefit as well. Really, I think at a high level, the important takeaway here is that we expect broad adoption across both PD-L1 negatives and positives patients in that frontline. Okay, great. Then in terms of just turning to launch. The PDUFA is in August 25th and for first-line GEA HER2 positive. Just wondering if you have any expectations in terms of near-term expectations for launch and how you expect that to translate to the sort of royalties that we've been seeing with BTC, but now how you expect that to change with GEA? Yeah. I think you mentioned it, but we're pleased to see the priority review. On August 25th, PDUFA for the sBLA. It's always nice to go into an sBLA with positive overall survival at the first interim. There's a lot of confidence in the quality and robustness of the data. As you mentioned, the drug has an accelerated approval in BTC, and it's been great to see the adoption from treating physicians, and there's a lot of overlap between that. That's particularly important as we want treating physicians globally to have experience with the drug. We expect fairly robust adoption. I think we're going to wait until the approval to get maybe more into those metrics and really defer that to Jazz and BeiGene to provide any sort of more granular guidance on that. We've been really pleased with some of the pre-launch activities and expect an on-time early approval for that molecule. Just looking forward for Zani on the sort of next steps or next indications that we should be looking for. There's the phase III EmpowHER trial, and Jazz has been saying it could be a $2 billion-$3 billion-plus opportunity being Ziihera. Just what will we see next? Where do you see expansion opportunity, and how are you thinking about that? Yeah. There's an enormous opportunity, we think. To your point, Jazz has provided some guidance of $2 billion plus. I would say, our opinion of that is that we lean into the plus. That guidance is a bit stale. There's been some, I think, very powerful data. You've seen from our partners the language and enthusiasm about the molecule. We expect a broad development program and I think we'll leave it to them to give any more specifics about additional plans for studies. We're really excited that there's this broad enthusiasm around all the partners that are touching the molecule and driving that forward. Specifically to your question on the EmpowHER-303 study in breast cancer, it's important to take a step back and look at the development of HER2 agents historically across the variety of histologies. Gastric has traditionally been one of the most challenging. The fact that we have a global randomized 3-arm study that definitively showed a very clear benefit, dethroning Herceptin, which no one had done before, in that setting gives us a lot of confidence about the breast cancer study. Jazz announced at J.P. Morgan earlier this year that based on some of the early data and their operational excellence, that they actually are seeing such a high demand for that study that they pulled in the timing for that. We're expecting a late 2027 or early 2028 top-line readout for that. It's a hugely exciting opportunity. HER2 is a phenomenal drug. It's really changed the standard of care for patients as that drug has marched earlier into starting in late-line metastatic, into front-line metastatic, and then into adjuvant and neoadjuvant breast cancer. Zani is set up to have the first prospective randomized data for patients after they progress. That we hear from physicians over and over again, there's just a dearth of data, and there needs to be some high-quality randomized data that help both patients and physicians make decisions about the right treatment. We're really optimistic about ZANI, particularly in breast cancer. Okay. Given that this is post-Enhertu, can we just briefly high level talk about why there wouldn't be any sort of sequencing issues with a two HER2 targeting agents, and is there a resistance mechanism or anything we should be thinking about? Yeah. It's a great question. The preliminary data that we have from the early phase I, there is some post-Enhertu experience, and we see great activity. The trial should help answer this question, but based on ZANI's biparatopic mechanism, and some of the clustering that it induces, we expect that there would be an opportunity to show a pretty significant benefit over T-DXd in that post-Enhertu setting. Okay, great. I think we can move on from the Ziihera topic and maybe just go to one of your later stage wholly owned assets right now, which is ZW191, your folate receptor alpha ADC. You presented data at AACR. Just want to get any feedback of, I know you're putting this up for sort of discussions with other companies or things like that, if there's any sort of update or when we should expect an update for that. I'll do my best to give you insight, but with our novel strategy around really doubling down on what we think this company is great at, which is sort of true de novo discovery through that phase I proof of concept, you should expect we're always talking to partners. We have a great dialogue with folks. There's a lot of interest across the pipeline. We're never really going to be in a position to give guidance on when and if there'll be partnering events. I can talk about is some of the feedback from physicians and KOLs, and our take on that GYN landscape in the late-line metastatic setting. I think it's a good opportunity to do so given the Tubulis data was presented at ASCO as well. 191 is clearly showing itself as a very active and very well-tolerated molecule. Just to remind folks, this is our wholly owned folate topoisomerase ADC with our custom topoisomerase payload and linker. We think that the early data, which was an update of the escalation, is really robust. We're seeing response rates that aren't seen by some of the other molecules, and a tolerability profile that seems, based on early data, to be a little bit better, a little bit lower on some of the marrow toxicity and some of the other key tolerability issues associated with the other topos in that class. That being said, it's a very crowded landscape. I think the Tubulis data was strong. We think our data is sort of in that same realm. This landscape continues to get more and more crowded, particularly in the topoisomerase side. Our expansion is fully enrolled. About 60 patients. We'll share that data when it's sort of appropriately matured. We always present only our data at medical meetings and peer-reviewed settings. You should expect that data to be available when it's sufficiently matured. We'll think that will help drive some of the strategic conversations that are happening in the background. Okay, great. In terms of what you just mentioned, the dose optimization cohorts are complete. What should we expect to see from that data, I guess? How much data should we be expecting to see? Do you expect any changes in the part two design or anything like that? As you mentioned, the dose optimization is fully enrolled. We're exploring two doses, 6.4 and 9.6. I would just mention, as I talk about those doses, if you look at the field, most folks who are using the regular exatecan payload or other very potent payloads are capped at a one, two, or three mg per kg dose, and we think the protein dose matters. We're really excited about the doses we're at. We'll let the data drive where we go with this and let that drive the strategic conversations that we're having. As I mentioned, it's about 60 patients, and we'll share that data when it's appropriately mature. We like to make sure that there's two scans on all the patients and let that be at a peer-reviewed setting. Okay. Got it. Also at AACR, you showed preclinical data for ZW191 in combo with other agents. Can you talk about why you think that this asset specifically is differentiated for combo, what we saw in that preclinical paper or that presentation, and what additional combos we might see? Yeah. It's a great question, and I'm glad I have the opportunity to talk about it. You don't always get asked about the preclinical data, but it's really important because it does help drive both our strategy and where we think where partners might be able to take this molecule. As I mentioned, the topoisomerase ADC world in particularly GYN tumors is getting quite crowded, combinations into earlier lines is going to be the name of the game. It's bigger market opportunities. There's opportunity to drive bigger, more robust benefits for patients. The challenge historically has been, if you look at some of the more advanced molecules, is some of the tolerability issues that they have. We think it's going to be a challenge for some of those molecules to successfully combine with either PARP or bevacizumab or chemos if you start talking about platinum sensitive, just based on the overlapping toxicity profiles. Again, while our data is very early, and we want to see a broader, more robust data set when the expansion's available to confirm those early findings, and we'll see what that looks like. We think based on the clinical tolerability profile that we're seeing and some of the early preclinical data, we do think there's an opportunity to potentially explore some combinations that aren't available to potentially some of those other topos. Okay. Got it. I guess lastly, on ZW191, it sounds like there's additional data ESMO GYN, so what should we expect there? Yeah. Data's in about two weeks, so I'm not going to front run it too much. I will just highlight maybe qualitatively what you'll see there. It is a subgroup analysis of the escalation. The team spent a lot of time building that asset. It is a very, very high-quality binder. We spent a lot of time focusing on creating a molecule that internalizes better than some of the other antibodies that are out maybe a little further ahead. You might expect to see, and what we wanted to see, is a relationship to folate expression. We think based on some of the bystander activity, we should see great activity across all patients, but we do want to see if there's a dose response. If that may create some opportunities to explore different and novel future development strategies in those different folate-expressing subpopulations. I think I'll probably leave it at that until we see the data, but that gives you a little bit of the background on design principles and what we might expect to see. Okay. That was very interesting. Moving on to ZW251, your GPC3 ADC, I guess just starting off, you're in phase I right now. Can we just get any expectations of when, I guess, we'll see data and what we should expect in that data? What would you consider exciting to move forward there? The ZW251 is a really exciting molecule, and there's some actually really interesting recent data from ASCO to point to that helps shape that field. Just to remind folks, 251 is a GPC3, same linker payload as the folate, which we think has really validated that payload, that custom payload that the team built a few years ago. That's being explored in HCC, and we recently announced an expansion into squamous lung, which we think is a very meaningful expansion opportunity. We don't provide guidance on timing of when we're going to release. I think the best thing I can say is we have a really phenomenal clinical team for early clinical proof of concept studies. We went from first patient to sharing data in about a year on the folate side, and we think there's an opportunity to repeat that pace, particularly on 251, where we're out in front. There's such a competitive and crowded field on the folate side in GYN tumors, but there's really a great opportunity to move quickly and explore how fast we can move this molecule forward. In terms of expectation settings, we're not going to give patient numbers or anything. We're moving through the cohorts quickly and have been really pleased with the enrollment. The important maybe benchmark setting data of this setting is probably from ASCO with the IMbrave study that Roche presented. It was a failed study of atezolizumab plus TKI versus TKI in that second line post atezolizumab-bev setting. That's probably the most robust prospective data that's been available in that second-line setting and provides a nice benchmark of what we want to clear. That both arms reported about a 5%-7% response rate and a four-month PFS really speaks to the enormous unmet need for patients in this setting, and serves as a reasonable benchmark of something we want to be meaningfully better than. Okay. Just two follow-up questions there. You said it would take maybe a year from starting to maybe see data. When did we start the study, just to give some context? The study started towards the back half of last year, late last year. Okay, got it. Yeah. Probably back half. Okay, got it. Yep. In terms of the safety aspects of your 191 differentiates on safety, do you expect anything there for your GPC3 specifically? I'm not going to guess about a tolerability profile. I think I'll let the data speak to that. We do think there's read-through. I kind of leave it at that. What I think maybe gets overly lumped in as just topoisomerase by investors too much, there are important differentiations between design philosophies, more potent, less potent topos, slightly differentiated linkers. We do think that matters. We're really pleased with the FolRa data and do think there's read-through given the overlap in design. In terms of any specific guidance on tolerability, I think we'll wait till the data's available. Okay, got it. In terms of, you also mentioned you're entering squamous, non-small cell lung cancer, and also germ cell. Just can we talk about the rationale behind taking the GPC3 into these specific indications and where the confidence is coming from? Yeah. We really have a robust understanding. Zymeworks is over 20 years old, and there's an incredible focus on the biology and understanding the patient population that might benefit from these therapies. Rather than it being first a market opportunity that we're chasing, it's driven based on the underlying biology and where we see expression, and based on the understanding of our molecule where patients might benefit. Squamous with almost 60% expression plus of GPC3 and some early data, including at ASCO, a Merck trial of sac-TMT showing a really interesting activity in squams. We think that there's sufficient rationale both preclinically and from the market opportunity to explore and add an expansion there. We'll definitely let the data drive future investment decisions, but certainly enough rationale based on what we understand about the molecule and as we clear cohorts to add in those squams. Germ cell tumors is, again, goes back to that comment I made based on the biology, is very high expressing GPC3. A little bit smaller of a market opportunity, but with a very heavy pediatric population. It's a patient population that needs new therapies, and it's the right thing to do to explore it there, and we think there is a market opportunity should we see a sufficient signal. Okay, great. For this ADC, similar to your 191, is there a sort of combo approach that you might be trying to go with? We saw ivonescimab showed also data in squamous non-small cell lung cancer, so just want to see if there's any combo for any opportunities. Yeah. No specific updates today on combos, but you might imagine as we explore squam lung, that's going to need to be longer term in combinations to explore earlier lines. There is probably an opportunity in the later lines for a monotherapy, but we're going to just have to see how robust that data is and if there's an opportunity to go head-to-head as a monotherapy, or it'll go straight into combination exploration. Okay, perfect. Now I think I'll move on to just the other assets in earlier stage. Just in general, it seems like 191 and 251 we've talked about, those are in phase I and they're continuing. There's other assets like ZW220 or ZW327 or other ones that are ADCs that seem to only be moved forward if there is external funding or partnership. I guess, number one, why are we not moving those forward? Number two, why are the specific 191 and 251 selected for Zymeworks specifically? Yeah, good question. Zymeworks is in a really privileged position of having an incredibly valuable partnered portfolio. We understand the value of our business based solely, before we even talk about adding in the incredible value we think that our R&D pipeline has, we understand the value of the royalties that we receive from our partners at Jazz and EcoR1 Capital, from J&J with pasritamig, which I don't think gets quite enough time given its promising data, and some of the earlier legacy royalties that are making progress. We are leaning into what we think that we're amazing at, which is that early discovery through that phase I proof of concept, and trying to rightsize the organization to make sure that this can really be a sustainable R&D company long term. We think that there's an incredibly competitive landscape, as we mentioned, on the ADC side. We were excited with our lead molecule to push 191 in. We think we validated a lot of the work that we've been doing for the past eight or 10 years on the ADC side, showed that the design principles preclinically actually translated to the clinic. Wanted to just make sure we had some external capital to help fund 220, particularly within NaPi2b, before we took another molecule into the guide setting. 327's in a similar setting. That's our Ly6E topo that we think, again, has a great opportunity, but given the validation that we've achieved from 191 and proving those out, and we hope soon with 251, we think that should be sufficient to drive partnering interest. We want to only drive those forward with external capital. Okay, understood. Just also in general, it seems like initially it was more ADC focus. Now we're also going into multi-specific antibodies and other types of engineering there. Can we talk about the rationale between not switching, but just moving towards that design? Yeah. I think the best way to answer that question is to sort of zoom out and give you a sense where the Zymeworks R&D strategy is headed. I think at a highest level, there's a focus on novelty. We are looking for opportunities to be highly differentiated. What this team has an incredible superpower at, and we have a real right to win, particularly as this landscape gets more and more crowded with China entering and moving so quickly. We are looking for highly novel, highly differentiated therapies. The topo landscape is crowded. It just is. That has pushed the team to start to think about where is the field going, rather than playing catch up. We think we have some really interesting paths with ZW191, with ZW251, where we're out in front with some of the other earlier topo molecules. It's important to be honest with folks that those are crowded. There is a huge opportunity for that next wave, where we're out with a real leadership. At AACR, we also presented, instead of a topo payload, some custom RAS payloads which is a really exciting opportunity right now with that target being validated by some of the amazing data with a pan-RAS inhibitor in pancreatic that I think a lot of us saw. A huge opportunity for multi-specifics to drive sort of a step change in how we treat some of the various oncology indications we're pursuing and an interesting portfolio of immunology. Really, I think at a high level, the rationale behind that is driving towards where we can be out in front as leaders with higher, more novel, both payloads on the ADC side and multi-specifics where we're having a significant push. Okay, that makes sense. Just touching on something you just mentioned, your RAS payload ADCs, post the ASCO data and post the AACR data that you presented, how are you planning to position these assets? How has your view on the space evolved? Any color there. First, I think it's important to stop and acknowledge the incredible accomplishment that RMC-6236 from Revolution Medicines has achieved. RAS has been holy grail for 50 or 60 years. It's been undruggable outside a very small sliver of the G12C. We were there, we were talking to physicians, we saw a standing ovation, and it's well-deserved. That being said, we think it's a first generation. There's opportunities to continue to improve for patients. The flip side of a 30% response rate is the 70% of patients that we need to do better for. We think that conjugating a custom pan-RAS payload to an antibody and helping avoid some of those systemic toxicities that you see with GI, with skin, with a variety of other tolerability issues, that there's an opportunity to get both better safety, which should enable more cons istent dosing, more time on top of RAS, and better combination opportunities to unlock some new histologies. Think colon in combination with EGFR. Think ensuring that you have full dose in lung. Again, it's an amazing accomplishment. What that data does for us is really just give us even more confidence in our platform that RAS is now a very validated target that can drive very meaningful benefit for patients. We think our approach and expertise around a conjugated pan-RAS to an antibody is custom-suited for the problem ahead. We're pushing those molecules towards IND as quickly as possible. Okay, great. Do we have timeline for the IND for that? We haven't provided a timeline yet, but we're excited to give guidance soon on that as those make more progress towards the clinic. Okay. Got it. Just two last questions before we wrap it up. ZW1528, your IL-33, IL-4 receptor alpha, the IND was pushed back to 2027 from previously 2026. Can you explain, I guess, why it was pushed back, maybe potentially external readouts from the IL-33, and what your team is trying to do with the additional time for the IND? Yeah. 1528 is the IL-4, IL-33 bispecific. The team has done an amazing job building that molecule and a deep pipeline of IL-4 bispecifics behind that we've talked a little bit less about, but is making progress. The IL-33 space has been a dynamic one and a volatile one over the last, call it 12 to 18 months. Three large pharmas had a variety of phase III readouts that we wanted to see. AstraZeneca, we were thrilled to see, announced multiple positive, and they defined as clinically meaningful benefit. We haven't seen that data yet, and we're eager to see that. Roche and Sanofi also presented their data recently. The team is interrogating that data closely to help really make sure, as we sort of customize our phase I, and which patients that includes, which subgroups of COPD that includes, after we proceed through the healthy volunteers. We just want a little bit more time to get some input on that. We're customizing that design now, and that slipped into 2027, but we remain enthusiastic about that molecule. Okay, great. Thank you so much. I think we're out of time. Awesome. Thank you.