RJ Tesi: Great question, Dan, and pretty easy to answer. This is where the enrichment criteria come in. You know we’ve been touting the fact that we only enrol patients with neuroinflammation and we define that by one of three blood tests or being APOE for five years. By doing a trial that matches the patient’s disease, neuroinflammation, with a mechanism of action, a drug that treats neuroinflammation, you actually make the trial work at six months better than the anti-amyloid trials. That is, to put it in heating terms, the statistical power increases because the variance decreases. So because there’s less noise, the data we get is cleaner. So whereas they need, it turns out if you look at the results they got, they would have needed about 700 patients per total, so 350 per arm, to actually have a positive trial at six months, but we only need 200.
So it’s all related to the enrichment criteria. We’ve always called it a little bit of our secret sauce and this is a good example of why it’s the secret sauce.
Daniel Carlson: Got you. That makes perfect sense, thanks. Mark, question for you on INKmune. The prostate market has certainly heated up with, in these radioconjugate companies, some of them have been acquired and some financing with great valuations, etcetera. Can you compare or just tell us how INKmune competes with radioconjugates?
RJ Tesi: Yeah, thanks Dan, that’s a very good question and plainly, they’re much further down the line than we are in their trials and getting their drugs licensed, but the fact is that radiopharmaceuticals are tough to deliver, just getting the isotopes and if you think about Pluvicto, the Lutetium-177 that they use for Pluvicto, there’s only one manufacturer of Lutetium-177 in the entirety of the United States and I think there’s probably only three globally. So you do end up looking, as we’ve seen with the Strontium-89 in Metastron, a challenge in getting the availability of the radioligand. The other problem, of course, is, or one of the other problems, is of course the short shelf life. Lutetium’s got a shelf life of, I think, 6.7 days or seven days.
So your manufacturing issues are very considerable and I think as these drugs get more widely used, we’re going to see bigger problems with that, but I guess that the real difference is the sort of recall effect that you get, which leads to off-target toxicity, even with these relatively well-tolerated drugs like Pluvicto. You’ve got bone marrow suppression in these patients become anemic and so that’s fine in the metastatic castration-resistant prostate cancer setting where you’ve got patients who are very far down the therapeutic line, but it does make them more challenging to deliver earlier in the treatment process and the great thing about INKmune is its complete lack of toxicity in the patients we’ve treated so far and in the animal models that we used beforehand.
So I think the great difference, if you wanted to look at one now, if we’re successful with INKmune, I see it moving earlier in the treatment paradigm. So you end up treating patients with early stage disease, which is where we are with many of the other immunotherapies. So that’s where I think the difference will be. We’ll have a wider population of less severely sick patients.
Daniel Carlson: Awesome. That’s great. Thank you. That’s good input. Thanks. And then one more question. RJ, just if you can comment, it seems like both INKmune and the Alzheimer’s trial, the enrolment seems to be on track. Can you just talk about the trends you’re seeing in enrolment right now?
RJ Tesi: Yeah, well, but I’ll start with INKmune. INKmune is actually, enrolment has been constrained by the FDA’s requests. In other words, they wanted, in the Phase 1 portion of the trial, 28 days between each patient in the cohort. So by definition, the first, getting all three cohorts done will take nine months. Now, there is some speed up because of the Bayesian design, because there is some overlap of the Phase 2 groups. But the bottom line is, we’ve had more patients actually contacting us who want to be enrolled in the trial than we have slots for right now. Now, knock on wood, let’s hope that continues when we get to the Phase 2 portion, where we have a little more flexibility in enrolment rates. But the bottom line is, prostate disease is common.
The patients are actually quite sophisticated in searching for clinical options and so they contact us as often as our clinical sites go looking for them, which is quite encouraging. Alzheimer’s disease is more interesting, as I said earlier, because all of our studies are in jurisdictions where the anti-amyloids aren’t approved. In fact, we’re only competing with clinical trial, other clinical trials. Now, there’s a lot of clinical trials in Alzheimer’s disease, including, both companies are running, Phase 3s and other trials. So there’s a lot of patients being consumed by the anti-amyloid trial. But as I said to Joel, XPro is just kind of an attractive drug. It’s a different mechanism. So we get a good listen. It’s safe. It’s a good mechanism.
I have to say, it’s not the — it’s rarely the patient that chooses on which trial to be in. They really follow the advice of their clinicians, but the clinicians like, kind of like what we’re doing and so far, so good is all I can say. I will say that we, every day we get up and we think of ways that we can speed enrolment and I think we’ve got some ideas and we’re pushing hard and so far, fingers crossed, toes crossed, everything’s going to work out as we’ve promised for the last two years, despite our frustrations with the FDA.
Mark Lowdell: I just like to say that Dan, I’ve been doing early phase clinical trials all my career, and I have never known a trial, either the XPro ADO2 trial or our INKmune trial in prostate cancer that has enrolled to schedule in the way that these two trials have and so we can be really confident about the outcome, the delivery time point, given the sheer enthusiasm for patients on both trials, which is, I say is remarkable in my experience.
