Conference Transcript - ZYME 2026-06-03

Phoebe Tan, Analyst — Khosla Ventures

Hi everyone, welcome to today. My name is Phoebe Tan. I am an associate on a Kashiwari's team and today I have the pleasure of hosting Zyme. And we have Scott Plashton here with the chief business officer. So I'll pass it over for any intro remarks. Perfect. Thanks for having us. Really

Scott Pashton, Other

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 and 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, and 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 partner's hands now in Vancouver. The company's at a really interesting and privileged point right now that has developed Xanadatamab with our partners JASNB1, 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 partner's hands. And so 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 so we're we're really privileged the company's in a great financial shape with with a robust balance sheet and is pushing forward a really interesting pipeline

Phoebe Tan, Analyst — Khosla Ventures

that we'll get into today awesome thank you so just starting with Zahara and the paper came out recently there's some subgroup analysis that we've been getting questions about so 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 so thanks for the question give me

Scott Pashton, Other

an opportunity to talk about my favorite topic so we're we're really really proud of the paper and the work that's gone into Zahira just to back up before we get into the some of the subgroup analyses you're mentioning from the from the recent New England and ASCO presentation I think the high-level takeaway is zanadatumab is the standard of care in frontline gastric for all patients you can see from the high level that it drove a meaningful benefit meeting 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 um subgroup analysis from from asco and mentioned in the new england the um the the the the outcomes by pdl1 status um as we know um a few years prior to to our top line results merck put out their keynote at 11 results which showed only a benefit in the pdl1 positive it really makes sense that zannie is going to drive a benefit across both subgroups um as we're um innovating on the her two side of it rather than a PD one side and so I think the 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 probably even more of consistent feedback from the ASCO meeting is that regardless of PD what PDL one status we would expect strong uptake there is some interesting biology that we can get into of Xanny Xanny does drive PDL one up regulation and so there's a lot of interesting theories about, you know, that may be driving some of the benefit as well. But really, I think at a high level, the important takeaway here is that we expect broad adoption across both PD-L1 negatives and positive patients in that front line. Okay, great. And then

Phoebe Tan, Analyst — Khosla Ventures

in terms of just turning to launch, so the PDUFA is in August 25th, and for first-line GA are two positive. And 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, you know, how you expect that to change with GEA? Yeah. So, um, I think you

Scott Pashton, Other

mentioned it, but we're, we're pleased to see the priority review. Um, so on August 25th, for the SPLA, um, it's always nice to go into an SPLA with, uh, with, you know, positive overall survival at the first interim. So there's a lot of confidence, um, in the quality and robustness of the data um as you mentioned there um the drug has an accelerated approval in btc and it's been great to see the adoption um from from from treating physicians and there's a lot of overlap between that that's particularly important um as we want treating physicians globally to have experience with the drug um we we expect fairly robust adoption i think um you know we're going to wait until the approval to get, you know, maybe more into those metrics and really defer that to JAS and B1 to provide any sort of more granular guidance on that. But we've been really pleased with some of the pre-launch activities and expect an on-time early approval for that molecule.

Phoebe Tan, Analyst — Khosla Ventures

Okay. And then just looking forward for Zannie on the sort of next steps or next indications that we should be looking for. There's, you know, the phase three Empower trial and there's jazz has been saying it could be a two to three billion dollar plus opportunity being zahara so just what's kind of what will what will we see next where do you see expansion

Scott Pashton, Other

opportunity and how are you thinking about that yeah so there's a enormous opportunity we think um to your point jazz has provided some guidance of two billion plus i would say um our opinion of that is that we lean into the plus um that guidance is is is a bit stale and there's been some um I think very powerful data, and you've seen from our partners the language and enthusiasm about the molecule, and so 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, but we're really excited that there's this broad enthusiasm around all the partners that are touching it, the molecule, and driving that forward. um specifically to your question on the empower 303 study in breast cancer it's important to kind of take a step back and look at the development of her two agents historically across the variety of histologies gastric has traditionally been one of the most challenging and so the fact that we have a global randomized three-arm study that definitively showed a very clear benefit you know 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 high demand for that study that they pulled in the timing for that. So we're expecting a late 2027 or early 2028 top line readout for that. And it's a hugely exciting opportunity. And HER2 is a phenomenal drug. It's really changed the standard of care for patients. As that drug has marched earlier into, you know, starting in late-line metastatic, into frontline metastatic, and then into adjuvant and neoadjuvant breast cancer, this, you know, ZANI is set up to have the first prospective randomized data for patients after they progress. And 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. And so we're really optimistic about any particularly in breast

Phoebe Tan, Analyst — Khosla Ventures

cancer. Okay. And given that this is post and HER2, 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 kind of is there a resistance mechanism or anything we should be thinking about? Yeah. So it's a great

Scott Pashton, Other

question the preliminary data that we have from the early phase one there is some post in HER2 experience and we see great activity the the the the trial should help answer this question but based on Xanny'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 trash in that post in her

Phoebe Tan, Analyst — Khosla Ventures

two setting okay great so i think we can move on from the zahara topic and maybe just go to one of your later stage wholly owned assets right now which is ew191 your folate receptor alpha adc um so you presented data at acr just want to get any feedback of i know you're putting this up for sort of um discussions with other companies or things like that how if there's any sort of update

Scott Pashton, Other

or when we should expect an update for that i'll do my best to give you a insight but um with our 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 kind of phase one 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 what I can talk about is some of the feedback from from physicians and kols um and our take on that um gyne landscape in the late line metastatic setting um and i think it's a good opportunity to do so given the tubulous data was presented at asco as well um 191 is is clearly showing itself as a very active and very well tolerated um molecule just to remind folks this is our wholly owned um uh folate topo adc with a custom with our custom topo payload and linker we think that the early data which was an update of the expansion of the escalation excuse me is 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 key tolerability issues associated with the other topos in that class um that being said it's a very crowded landscape i think the tubulus data was strong we think our data is sort of in that same realm but this landscape continues to get more and more crowded uh particularly in the topo side um our expansion is fully enrolled about 60 patients um and so we will uh we'll share that data when it's sort of appropriately matured um we always present only uh our data at medical meetings and peer-reviewed settings so you should expect that data to be available you know when it's sufficiently matured um and we'll think we'll that will help drive you know some of the

Phoebe Tan, Analyst — Khosla Ventures

strategic conversations that are happening in the background okay great and in terms of what you just mentioned the dose optimization cohorts are complete so is there anything what should we expect to see from that data i guess how much data should we be expecting to see and do you expect any changes in like the part two design or anything like that yeah so the as you

Scott Pashton, Other

mentioned the the dose optimization is fully enrolled we're exploring two doses 6.4 and 9.6 I would just mention you know as I as I talk about those doses if you look at the field most folks who are using sort of the regular exotecan payload or other very potent payloads are capped at sort of a one two or three mix per kg dose and we think the protein dose matters and so we're we're really excited about the doses we're at we'll let the data drive what that where we go with this and and let that drive the strategic conversations that we're having as I mentioned it's about 60 patients and you know we'll share that data when it's appropriately mature we like to you know make sure that there's two scans on all the patients and let that be at a peer

Phoebe Tan, Analyst — Khosla Ventures

reviewed setting okay got it and then also at AACR you showed pre-clinical data for ZW191 in combo with other agents so can you talk about why you think that this asset specifically is differentiated for combo and then what we saw in that pre-clinical paper or that presentation and

Scott Pashton, Other

what additional combos we might see yeah so it's 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 pre-clinical data but it's um 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 the as I mentioned that the topo ADC world in particularly gyne tumors is getting quite crowded and so 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 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 Bev or Or chemo's if you start talking about platinum sensitive Just based on the overlapping toxicity profiles. So again while our data is very early And we want to see them, you know a broader more robust data set when the expansion is 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.

Phoebe Tan, Analyst — Khosla Ventures

Okay, got it. And then I guess lastly on ZW191, it sounds like there's additional data at ESMO-GYN. So what should we expect there?

Scott Pashton, Other

Yeah, so data is in about two weeks, so I'm not going to front run it too much. I will just kind of 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 you know maybe a little further ahead and 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 and if that may create some opportunities to explore different and novel future development strategies in those different folate expressing subpopulations so 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

Phoebe Tan, Analyst — Khosla Ventures

principles and what we might expect to see okay that was very interesting um so then moving on to zw251 your gpc3 adc i guess just starting off you're in phase one right now um is there can we just get any expectations of when i guess we'll see data and what we should expect in that data and then what would you consider exciting to kind of move forward there?

Scott Pashton, Other

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 and that's being explored in in HCC and we recently announced an expansion into squamous lung which we think is a very meaningful expansion opportunity we we don't provide guidance on timing of when we're gonna release I think the best thing I can say is we have a really a phenomenal clinical team for early clinical sort of 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 to to repeat that pace particularly on 251 where we're out in front there's you know such a competitive and crowded field on the folate side and GYN tumors but there's really a great opportunity to move quickly and and explore how fast we can move this molecule forward in terms of expectation settings you know 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 sort of maybe benchmark setting data of this setting is probably from ASCO with the Embrave study that that Roche presented it was a failed study of Atezo plus TKI verse TKI in that second line post Atezo 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. So that, you know, the both arms reported about a five to seven percent 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

Phoebe Tan, Analyst — Khosla Ventures

meaningfully better than. Okay. So just two follow-up questions there. You said it would take maybe a year from starting to maybe see data so can we just when did we start the study just

Scott Pashton, Other

to give some context uh the study started towards the back half of last year late last year okay

Phoebe Tan, Analyst — Khosla Ventures

got it it's probably back half okay got it and then um in terms of the safety aspect so you know your um 191 kind of differentiates on safety do you expect anything there for your gpc3 specifically

Scott Pashton, Other

um i'm not gonna i'm not gonna guess about a tolerability profile i think i'll let the data speak to that um we do think there's read through okay i kind of leave it at that um the the team has a very differentiated you know and and what i think maybe gets overly lumped in as just topo by investors too much there are you know important differentiations between design philosophies more potent less potent topos slightly differentiated linkers and we do think that matters and um you know we're really pleased with the folate data and do think there's read through given the overlap and design uh but in terms of any specific guidance on tolerability i think We'll wait until the data is available.

Phoebe Tan, Analyst — Khosla Ventures

Okay, got it. And then in terms of, you also mentioned you're entering squamous non-small lung cancer and also germ cell. So just can we talk about the rationale behind taking the GPC-3 into these specific indications and where the confidence is coming from?

Scott Pashton, Other

Yeah. We really have a robust understanding of, you know, Zymerx 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. So 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. So squamous with, you know, almost 60 percent expression um plus of gpc3 and some early data including at asco a merck trial of sac tmt showing a really interesting activity in squames we think that there's sufficient rationale both pre-clinically and from the market opportunity to explore and add an expansion there so we'll um we'll definitely let the data drive um future investment decisions but certainly enough enough rationale based on what we understand about the molecule and as we clear cohorts to add in those squames. 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.

Phoebe Tan, Analyst — Khosla Ventures

Okay, great. And then for this ADC, similar to your 191, is there a sort of combo approach that you might be trying to go with? We saw Ivan Eskamab showed also data in squamous small cell lung cancer, so just want to see if there's any combo for any opportunities.

Scott Pashton, Other

Yeah, no specific updates today on combos, But you might imagine as we explore squame 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.

Phoebe Tan, Analyst — Khosla Ventures

Perfect. So now I think I'll move on to just the other assets in earlier stage. So just in general, it seems like 191 and 251, we've talked about, those are in phase one and they're continuing. There's other assets like 220 or 327 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? And then number two, sort of why are the specific 191 and 251 selected for Zyme specifically?

Scott Pashton, Other

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 on, 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 V1, from J&J with Passeritamig, 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 one proof of concept and trying to right size 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 guy inside and so uh you know we were we were excited with our lead molecule to push 191 and we think we validated a lot of the work that we've been doing for the past you know eight or ten years on the adc side showed that the design principles um pre-clinically actually translated to the clinic um but wanted to just make sure we had some external capital to help fund 220 particularly with uh with the nappy 2b um before we took another molecule into the gyne setting and 327s in a similar 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 you know we hope soon with 251 we think that should be sufficient to drive partnering interest but we want to only drive those forward with with external

Phoebe Tan, Analyst — Khosla Ventures

capital okay understood and then it just also in general it seems like initially it was more ADC-focused, and 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

Scott Pashton, Other

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. And 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 you know china entering and moving so quickly we are looking for highly novel highly differentiated therapies um the topo landscape is crowded it just is um that has pushed the team to start to think about where is the field going rather than playing catch-up so you know we think we have some really interesting paths um with those you know 191 with 251 where we're out in front with some of the other earlier topo molecules um but it's important to be honest with folks that those are are crowded um there is a huge opportunity for that next wave where we're out with with a real leadership so at AACR we also presented instead of a topo payload some custom RAS payloads which is a which is a really exciting opportunity right now with that target being validated by some of the amazing data with a pan-ras inhibitor and pancreatic that I think a lot of us saw there's also a huge opportunity for multi specifics to drive sort of a you know, a step change in how we treat some of the various oncology indications we're pursuing and an interesting portfolio of immunology. So 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 multispecifics where we're having a, you know, significant push.

Phoebe Tan, Analyst — Khosla Ventures

Okay, that makes sense. Just touching on something you just mentioned, you know, 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? And yeah, any color there.

Scott Pashton, Other

So first, I think it's important to stop and acknowledge the incredible accomplishment that 6236 from Evolution of Medicine has achieved. You know, RAS has been a holy grail for 50 or 60 years. It's been undruggable, you know, outside a very small sliver of the G12Cs. and so you know we were we were there we were talking physicians we saw a standing ovation and it's well deserved um that being said we think it's you know a first generation there's opportunities to continue improve for patients um you know the the flip side of a 30 response rate is the 70 of patients that we need to do better for and we think that conjugating a pan 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 to get both better safety which should enable more consistent dosing more time on on on on top of rass and better combination opportunities to unlock some new histologies so think colon in combination with egfr um think ensuring that you have full dose and lung so again you know it's an amazing accomplishment what that data does for for us is really just give us even more confidence in our platform that rass is now a very validated target that can drive very meaningful benefit for patients. And we think our approach and expertise around a conjugated pan-ras to an antibody is custom suited for the problem ahead. And so we're pushing those molecules towards IND as quickly

Phoebe Tan, Analyst — Khosla Ventures

as possible. Okay, great. And do we have a timeline for the IND for that? We haven't provided a

Scott Pashton, Other

timeline yet, but we're excited to give guidance soon on that as those make more progress towards

Phoebe Tan, Analyst — Khosla Ventures

the clinic. Okay, got it. Just two last questions before we wrap it up. So ZW1502, your IL33, IL4 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 IL33, and what your team is

Scott Pashton, Other

trying to do with the additional time for the IND? Yeah, so 1528 is the IL4, IL33 by specific. The team has done an amazing job building that molecule and a deep pipeline of IL-4 by specifics behind that 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 3 readouts that we wanted to see. astrazeneca we were thrilled to see announced multiple positive and they they define they just um defined as clinically meaningful benefit we haven't seen that data yet and we're eager to see that um roche and sanofi also presented their data recently the team is is interrogating that data closely to help really make sure as we sort of customize our phase one in which patients that includes which subgroups of cop that includes after we proceed through the healthy volunteers We just want a little bit more time to get some input on that, and we're customizing that design now, and that slipped into 2027, but we remain enthusiastic about that molecule.

Phoebe Tan, Analyst — Khosla Ventures

Okay, great. Thank you so much. I think we're out of time.