Brian DeSchuytner: Sure. Maybe I can take that. I think there’s 2 companies that are out there in the B7-H4 space, Seagen and GSK Hansoh. So when you think about Seagen and the classical first-generation ADC platforms, we’ve compared Dolasynthen ADCs versus the VC MMAE ADCs extensively, preclinically. And have shown preclinically that our platform can deliver payload to the tumor much more efficiently and effectively. And in addition, we’ve shown in our past clinical presentation that our payload appears to avoid the severe neutropenia and peripheral neuropathy that does tend to be dose-limiting across MMAE programs. When you move to Hansoh GSK and AZ, frankly, those are all using payloads. There’s increasing evidence from conferences just this year that TOPO1 pretreated patients can develop resistance to payloads.
And when you look at this landscape and in particular, sort of the faster market and largest opportunities in breast cancer with a HER2 on TRODELVY becoming standard of care, we believe this could be a consideration. And frankly, I think we believe this is also evidenced by some commentary about focusing on gynecologic tumors for that ADC. I think another consideration is just the hematologic toxicities that you see for TOPO1s that are dose-limiting in similar ways.
Ashiq Mubarack: Maybe one more on XMT-2056. You’re obviously reducing the dose. I guess what gives you confidence you’ll be able to strike a sort of balance between HER2 coverage but not overstimulating the STING pathway, which might, of course, cause some immunologic safety issues. I guess some color on your thoughts on the therapeutic window might be helpful here.
Martin Huber: We’re not going to go into detail here, but I think what’s important is when we look at the amount of staying agonists and the effects downstream in human systems, it’s much more sensitive. So essentially, the idea is that you’ll shift it. But we believe that evidence of activation at the scale level will also be shifting as well so that it should move — so basically, the therapeutic index shouldn’t fundamentally change. It just should shift to a lower dose range. At this point in time, some of that data, we’re not — we need to discuss how we’re going to have that data available. That will be part of our January discussion.
Operator: The next question comes from Kaveri Pohlman of BTIG.
Kaveri Pohlman: Can you provide any additional color on what your 2026 cash runway include? Does it include any additional trials beyond dose expansion for 1660 and Phase I for 2056?
Brian DeSchuytner: So thank you, Kaveri. Our cash runway guidance is based on our current operating plan commitments, which include the early clinical development of both 1660 and 2056.
Kaveri Pohlman: And for 2056, can you tell us about the HER2 epitope. How validated it is? And PERJETA doesn’t work well if patients are retreated with it, is it something that’s known for 2056 epitope?
Brian DeSchuytner: So maybe I’ll take that. The HER2 epitode is distinct from that targeted by either pertuzumab or Herceptin. But it’s obviously on HER2. Yes.
Martin Huber: It does not cross react with those sites.
Kaveri Pohlman: Correct. But is it known about PERJETA — it doesn’t really work in patients if you retreat it, whereas Herceptin, you can keep giving patients even if they progress, they still respond. Is it something — why is that? And if your epitope had similar biology as Herceptin?
Martin Huber: Sure. We intentionally targeted a different HER2 epitope because in principle, we should be able to target patients who have previously undergone treatment with a HER2 paradigm. So it was part of the thinking was to intentionally go to a different part of the antigen.
