Stephen Willey: Okay. And then maybe just one quick one on HERIZON, I think one of the narratives around the KEYNOTE-811 data was that the control arm outperformed what was observed in ToGA and I guess that’s a byproduct of improved HER2 scoring, et cetera. But just wondering how you feel about the statistical powering when you go back to the underlying plan and kind of plug in a higher than anticipated PFS and OS in the control arm. Thanks.
Ken Galbraith: Yes. I mean, obviously, we haven’t seen all the data from KEYNOTE-811. We’ve seen as much as we can in the European Review, and I imagine there’s going to be more disclosed next year, either through the FDA process or by the sponsor of the study. I think it is a little hard to know what to make of that study, because there’s some disclosures on ITT, and there’s some disclosures on only the labeled indication, which is different. So it’s hard to understand that, obviously the recruitment of that study was skewed a little bit differently than we might have thought a real world population would be. So we’re not sure what to make about that as well. I think from our standpoint, if we look at the control arm and the ITT population and look what you saw from not really an ORR perspective, but you look at a PFS perspective, from median-PFS, it was around seven months.
So a little bit better than ToGA, but very consistent with the assumptions that we use in our physical design if you look through what we disclosed previously around this physical design. So we didn’t see anything in the active control arm of KEYNOTE-811 that makes us think that we’re – our design was not consistent with what we expected. So I think that part of that study gave us increased confidence in our clinical design. So that’s great. And obviously the comparison from the triplet in that study and its limited ability to drive OS so far, and its limited ability to really show benefit in the PD-L1 negative population gives us more confidence, obviously, in our ability to have a successful study and really be the choice of therapy in the first line GEA patient population, regardless of PD-L1 status, it’d still be our goal.
Stephen Willey: Very good. Thank for take the questions.
Operator: Thank you. [Operator Instructions] Our next question comes from Brian Cheng from JPMorgan.
Brian Cheng: Hey guys, thanks for taking my call this afternoon. We spoke a lot about your thoughts around the strategy with your ADCs in the pipeline in the past. When you think about ZW251, I’m just curious, do you see this asset as an asset that you can potentially take it all the way to the finish line or is this asset something that you want to see proof of concept first and then engage a partner to partner it off, given the indication or target? And then on top of that, just a housekeeping question, you’re looking at your INDs that are in the plan with two programs rolling out next year and also to after in 2025. How should we think about your expense trajectory and any color that would be super helpful for us from the modeling perspective. Thank you.
Ken Galbraith: No, two good questions. I think strategically on the portfolio, and we’ve tried to be very transparent about this, so investors can understand the rationale and obviously the prospects of the entire 5 by 5. And it also makes it easier for us to have very open and active discussions with potential collaborators. So you can see that at least with the four agents we’ve nominated now, there is a bit of a therapeutic concentration around both on the ADC and multi-specific side around focused on gynecological cancer patients and also on lung cancer patients. And that’s not unintentional. Those are two areas where we think we could make some strides with the agents we have both on T cell engagers and on ADCs in those areas.
I think when you look at other areas that we have experience in with zanidatamab, definitely on the GI side, between GEA and BTC, it made sense for us to look for an opportunity that was consistent with some of our experience. So HCC was a natural thing for us to look at. We obviously look for a less unencumbered and proven space. So I think GPC3 as a target is well understood. But I think we have the first chance to take an ADC approach to HCC with a TOPO payload and we’re excited about that for GPC3. So I think there was some sense that we have some experience in the GI space. HCC is something that we can broaden into a little bit, but we definitely have a concentration in gynecological cancer and lung cancer that when we talk to potential partners about multiproduct collaborations, it’s obviously around those therapeutic categories.
HCC is probably the one opportunity in GPC3 that we have the very active interest in collaborating, but probably more of a compelling reasons to hopefully hold on to that one for longer until we see clinical data. Both ADCs and multi-specifics are areas of interest that we see continue growing. We continue to see value attributed in transactions to quality assets at preclinical or early clinical stage that those values continue to go up, and we think that’s going to continue. So we have the capital and talent and infrastructure to be able to execute these programs on our own. But it doesn’t mean, we don’t have discussions about putting ourselves in a better position with a strong collaboration, either on a product basis, a multiproduct basis, or around that therapeutic concentration in gynecological cancers, lung cancer, or GI.
Moving forward, obviously moving things from preclinical into clinical studies takes on some additional cost. I think we’ve worked really hard this year and last year to build an infrastructure that’s a little more nimble and a little more cost effective than maybe we had when we were developing zanidatamab. So I feel very comfortable with the cost efficiency we’ve done in that infrastructure to be able to move quickly at a very cost effective way, and in a way that’s much more recruiting patients outside the United States and inside the United States, not just for cost purposes, but to try and get access to patients more quickly and also to patients who might be of a higher quality because they have fewer pretreatments available to them.
So that’s a strategy we’ve been working on since last year. If we’re right, we’ll be able to execute all five of these clinical programs in a very fast nimble way, in a very cost effective manner and generate meaningful data from the very first [indiscernible] we’re working on hard and we’ll see – we’ll get a chance over 2024 and 2025 to see us put that into action.
Brian Cheng: And just any thoughts or early color on how we should think about the expense projection given the two INDs and the two INDs in 2024 and 2025, respectively?
Ken Galbraith: Yes. I think right now, obviously, we’re – for this year, we’re looking at spending 20% odd of the cash balance we started the year with, obviously, that’s going to go up with more programs. But some of these preclinical programs, in terms of doing GMP and GLP tox are a sizable investment as well. So I think you’ll see the cost structure go up just because the number of programs that are either in preclinical or clinical is getting higher. And if we assume there’s no new collaborations and partnerships that will be the case. We feel very comfortable right now with moving all five of those ahead absent collaborations and partnerships, and obviously partnerships and collaborations and milestones from zanidatamab approvals will be things that we’ll rely upon to think about beyond 2026.
So I think you’ll see – we’ll give some financial guidance early in 2024 – about 2024. So you’ll likely see an increase from our cost structure because of the level of activity and size of the product portfolio, but not to a degree that we can’t handle that with our current cash runway.
Brian Cheng: Great. That’s super helpful. Thanks, Ken.
Ken Galbraith: You’re welcome. Thank you, Brian.
Operator: I’m showing no further questions at this time. I would like to turn it back to Ken for closing remarks.
Ken Galbraith: That’s great. Thank you. Thank you everyone for listening today. Obviously, we felt very encouraged by our progress to date through 2022 and year-to-date in 2023. And inside the company, we’re as excited as ever about the future of Zymeworks and what 2024 and 2025 holds for us. We’re very much looking forward to reporting our continued progress against our key priorities. During the remainder of 2023, because we’re not done the year yet, and into what we think will be a really exciting 2024 for us throughout the entire product portfolio. And with that, I want to thank you again for joining us. Appreciate your support and have a wonderful rest of your day. Thank you.
Operator: Thank you for your participation in today’s conference. This does conclude the program. You may now disconnect.
