Highlighting another potential catalyst RE therapy - this is the...

Highlighting another potential catalyst RE therapy - this is the transcript from Q3 2023 Earnings Call, Oct 18, 202319/10/23.

Shane Storey
I might start with Colin please and the SELECT data. The first question there is, look, our first impression here is that the PSA responses in the higher grade AEs both look a little bit lower than what we've seen in previous studies. So, Colin, I wondered if you could tell us, are there any significant differences in the patient population there that we should have in mind?And then maybe as a follow-up, conceptually, do you think you could possibly dose higher than the, I think, the 76 millicuries that you're currently using?
Colin Hayward
Yes, Shane. Look it's -- this is a data snapshot. We've certainly seen, and you asked about the significance, we haven't done statistics on these. But clearly the AE profile looks a lot more encouraging. I think this is reflective of the second-line metastatic population, a patient group with much better marrow reserve than before -- than the earlier studies in patients who are very advanced.I think what we need to do is continue to follow up the patients. There's still a number of patients in follow-up, and we've seen some later PSA responses. So we need to understand the efficacy and how that might relate to dose. Approximately, the dose is a 45 millicurie per meter squared dose given as a set free. So I think we need to see the final activity data going forward.
Christian Behrenbruch
Yes. Can I -- Shane, just before you go on, can I just chime in?. I mean, you have to go back to the Phase II trial data and remember that those were pre-palliative patients. I mean those were very -- those were super-heavily pre-treated patients that had very little hematologic capacity. So now, we're treating patients in a much more -- much earlier setting.And just like we've seen in the recent Pluvicto results that came out in advance of ESMO, healthier patients are resulting in fewer AEs. And I would go so far as to say that although it's a relatively small data set, it's 30 patients enrolled, 28 patients counted. From a safety data set perspective, it's still a good size data set, and it's a fixed dose. It's not a dose escalation. So what you're seeing is a competitive AE profile to other agents in that setting.And then I think we put some -- so we put some -- so we think that SELECT goes a good way towards dispelling this issue of toxicity. And in fact, when you look at the comparative biodistribution, you can see just how much more targeted the antibody-based approach is.And then, the other thing regarding PSA, we've always said and it's pretty well documented out there in the public domain that doing a comparative PSA profile between a small molecule and a biologic isn't going to be straightforward. The reason why we put out 3 case studies showing very different levels of disease burden and that biodistribution element that was part of the study, is it just shows you how late some of those PSA nadirs are, like a year, a year before you hit rock bottom on PSA.So, we're going to have to have -- as we go through and not only read out this study in terms of PSA and PFS, but as we go full throttle into GLOBAL, how we monitor PSA in the longer window is going to be really important for this agent.Shane StoreyYes. I was going to ask you, actually, mechanistically it seems early, I mean, the early data from both small molecule and antibody, if you put it together, I mean, it seems to be suggesting that an antibody-mediated sort of therapy tends to have, I guess, more modest PSA responses initially, but then longer survival. So mechanistically, I was going to ask you to help explain that and reconcile that for us.
Christian Behrenbruch
Well, it's just because of the retention of the agent. So if you compare internalization, retention and excretion of lutetium, the lutetium just hangs around a lot longer, and that has a very different radiation biology profile in turn than the small molecules do. And that's why we're seeing some of these incredibly long and slow PSA drops.And that's just something that you don't generally see in small molecules. And that's the reason why the dosing regimen for small molecules tends to be 6 to 8 weeks apart as a way of kind of throttling that treatment, whereas our strategy is about a very deep and aggressive treatment on the front-end that we hope, and of course, we've now got to show it in a randomized study that we think is going to potentially lead towards a more durable response in patients.And just the fact that we are tracking PSA nadirs out to a year, I mean I think it's going to be very exciting when we do actually have the PFS data for this agent because we are -- we will read out PFS for this study. I imagine it'll come in sometime in the new year, early in the new year. But it's a little hard to predict just because some of these patients have been hanging around for a long time.