Ken Herrmann: Thank you, Oliver. Always good to be back at UroToday.
Oliver Sartor: Well, you've just given a beautiful talk, actually a couple talks at APCCC, looking at some new targets and tracers. And I wonder if you might give our audience a little bit of an overview so they can understand the essence of your presentation in Lugano.
Ken Herrmann: Indeed, it's PSMA, PSMA-PET and PSMA-radioligand therapy who got nuclear medicine and theranostics to the APCCC. And I'm even more proud that now a couple of years later, we're even asked to think beyond PSMA.
And as you mentioned, I had to talk one of them in the translational science symposium, the second one in the very short eight-minute big APCCC stage. And what I tried to do is because they're 10 new targets currently explored beyond PSMA and prostate cancer. And I try to differentiate them.
So I took my three winners and this is very, very subjective, and focused there in the clinical part of the discussion. And then second tier, what I call it, I spent quite some time on the translational Congress.
Oliver Sartor: Well, let's hit the highlights and hear your thoughts, because I think a lot of people are interested in how you're thinking these days.
Ken Herrmann: To be honest, it's difficult to pick. It's early times. Initially, my talk was actually was named Near Term Clinical Implementation. To be honest, none of them are really near when we think about near, one or two years from now.
But I think we do have three targets which are currently hot and exciting enough to expect that maybe in four to five years, we really have a new therapeutic approved. My top three so far are ACP3. A target the two of us have talked about a lot. The second one I like a lot is actually STEAP1, STEAP2, currently explored also outside of radioligand therapy and of course B7-H3. It's difficult to talk about prostate cancer and new radioligand therapy concepts without targeting B7-H3 currently.
Oliver Sartor: Okay. So let's take them each in turn. So ACP3, I think we're all very familiar with. And now Rayze is doing the development. It's super clean. And the truth is that it looks like a really nice ligament that doesn't have any salivary uptake and it shoots to the kidneys. When do you think we might be able to hear more about ACP3?
Ken Herrmann: So first of all, you took all the steam away from ACP3. Everything you said is absolutely correct. There's maybe one thing I want to add. It might even have a higher affinity than PSMA.
So we have seen quite exciting data just recently published from Backhaus et al. in European Urology and really confirming what you said, also showing that in a significant amount of patients, the information is at least complementary to what PSMA has. Sometimes it's really ACP3 positive and PSMA negative.
And now when do we hear something? I think RayzeBio, and it's only one of them. I think that a couple of other companies are also now jumping on the ACP3 train, but they're really now working very hard to start the first activity/dose escalation trial. And I think the first patient in will be definitely in 2026. So for me, if you ask me one of the targets to watch, it's very difficult for me to imagine that this is not going the whole way to clinical approval.
Oliver Sartor: Good. How's the retention on the ligand? Do you have pretty good retention?
Ken Herrmann: So they haven't shared any data officially. That some things I have seen, including lutetium, it looks very, very promising. Now, I haven't seen a full dosimetry really where you can now talk about what is a tumor resilience time, but it really looks more like a PSMA than let's say a FAPI-46. So the reason mentioning it, we talk about days, not hours regarding the tumor retention time.
Oliver Sartor: Well, that's good. If it's days, not hours, then it should work. All right. So let's talk about B7-H3 for a second. Now B7-H3 is a great target. We started to get a little imaging data emerging from the muddy waters here, but tell me a little bit about B7-H3 and where you see it in prostate.
Ken Herrmann: So a very similar name of B7-H3, by the way, is CD276. It's immune checkpoint protein. It's a direct cousin of PD-L1, and it's a driver of aggressiveness, which makes it, I think, very interesting.
There are two different isoforms. I think one of them, the 4L form is the one which is highly expressed in tumor surface. So in case we really want to target B7-H3, it's probably better if you have one which is selective for the 4L isoform.
Where are we currently? We can learn a lot from ADCs because there are quite some compelling ADC programs currently in clinical translation, also inside prostate cancer. And we can say that there is at least one of them currently with an IND filed.
To be honest, we cannot talk about, and I'm not able to show you imaged examples yet because they will be shown at ASCO 2026. But I can tell you that this is, again, I think a very, very clean, nice biodistribution, not completely zero salivary gland uptake, but much, much less than what we have seen before for PSMA.
Oliver Sartor: That's good. Now, this is not going to have a little binding pocket. So you're going to have to use technology other than the typical small molecule. What type of molecules are being targeted to B7-H3?
Ken Herrmann: So I think there are different approaches to this. One of them is a mini protein. That's the one where an IND was recently filed. I'm not sure if their patient was already included or not. But also the Mariana, now Novartis-on technology, they also have certain proteins which really have the cyclic proteins really bind to the receptor.
Oliver Sartor: Terrific. All right. And you have a third favorite target, and that is ... Oh, gosh, now I'm going blank. Ken, what's your third favorite target right now?
Ken Herrmann: It's actually two. It's STEAP1 and STEAP2.
Oliver Sartor: STEAP1 and STEAP2. That's right.
Ken Herrmann: And it's both of them are ... So STEAP actually stands for Six-Transmembrane Antigen of prostate, either one or two. Both of them are membrane bound and sitting on the cell surface. I think this is very interesting. Both of them are currently explored also for ADCs and BiTEs. And nevertheless, they seem to be very, very clean targets.
And I've also seen, if I remember correctly, one imaging tracer from Memorial Stone Kettering published in 2019. It's actually, I think back then it was an antibody, but it looks very, very nicely and shows you that again, there's almost no cellular gland uptake.
It's important to mention that there are obviously BiTEs for both of them currently explored. One of them I think is in ADCs by the way, but there's a big program now currently ongoing with AstraZeneca trying to put STEAP2 directed ligand therapy into humans. For me, these are the three targets definitely to watch.
Oliver Sartor: Wow. Well, those are three really good ones. I might mention that the STEAP1 bispecific is in phase three and wrapping up the phase three. They've had strong preliminary data with the Xaluritamig, which is a really strong molecule. Kevin Kelly's been leading that trial, and it looks quite positive to me from the preliminary data. Of course, the phase three, everything's on the table. You don't know.
Ken, before we wrap up, just a little bit more about some of the, I'm going to say lesser known targets. If you drop down below the first three, first four you've listed, what other ones are catching your eye a little bit?
Ken Herrmann: No, I mean, I talked about a couple of other targets. I think one of them I think is quite interesting, CD46. It's a very interesting program actually from UCSF. And to be honest, I did not know much about it until I really read about it now, but I think it's very compelling. Again, a very clean, no real cellular ligand uptake.
I am also highlighted HK2, even so for some reasons it's currently, at least for now, deprioritized in the clinic development targeting radioligand therapy, but it's a very promising target obviously for the bispecifics. I'm going to talk about, or I talked about DIS3. I mentioned FAP, even though I'm not a big fan of FAP for prostate cancer, and about GRP.
And I also fully declare that I probably could have also talked about PARPi, about SSTR2 and PROP-2. But again, eventually you need to make a cut and you need to prioritize. And these are my personal decisions. I might regret my choices in two or four years from now.
Oliver Sartor: Well, Ken, you've always had a good notice for what's going to be next and always enjoy listening to you. Before we wrap up, are there any final words you'd like our listeners to be able to hear? Any wrap-ups that you think could be important?
Ken Herrmann: I really hope that I will be re-invited to APCCC in two years because then I think my initial talk title, Near Term Clinical Implications, will be more timely. I'm very convinced that in two years from now, we will have one, two, or maybe even three programs very close to being clinically approved. Overall, exciting times for prostate cancer and radioligand therapy. And I think I'm very convinced now that the time beyond PSMA has now finally begun.
Oliver Sartor: You know, Ken, I agree with you. These next couple of years are going to be extremely exciting. We have big programs launching for all of these targets. I'm going to be watching with a great deal of interest and hopefully participating in some of the trials myself. And all we want is for patients to benefit, and that's where we both when the rubber meets the road.
Ken Herrmann: I like when you say you're watching. This means more watching either the first row or watching with the steering hand, the steering wheel in your hands. Really, Oliver, this is amazing what you have done in the last 10, 15 years or maybe even longer. And I have zero lack of confidence that this is not going to change the next five years.
Oliver Sartor: Well, we're going to keep working to make patients better. Thank you, Ken. Appreciate all your contributions to the field.
Ken Herrmann: Thank you.