Dr. RJ Tesi: So, good question, and I’m going to answer it in a series of statements. First of all, I’m not predicting three months our trial is six months. Three months is pretty quick. We expect robust results after six months. Now let’s talk a little bit about the biomarkers. Our biomarkers of neuroinflammation in the Phase II trial are enrichment criteria. In other words, they’re things you need for enrollment. The FDA, I’m not convinced that the FDA will be, will accept biomarkers of neuroinflammation as a biomarker of Alzheimer’s. What they will accept are biomarkers of what they consider Alzheimer’s, which are amyloid, tau, maybe GFAP, which is glial fibrillary acidic protein, a biomarker of astrocyte. Now, the good news is there’s very good blood test for all of those, and I predict that we will actually show a decrease in those biomarkers in the Phase II trial in patients who get XPro.
So, my bet is, is that, what we’ve got is we’re going to be focused on patients who have neuroinflammation because that’s how the drug works. But we don’t think that the FDA — we make it surprised mind, but we don’t think the FDA will actually focus on neuroinflammation as a response. They’re going to stick to the biomarkers they know, and they know amyloid and tau, and they might be interested in GFAPs, and I don’t think they’ll be interested in NfL neurofilament light chain in Alzheimer’s. Those are my predictions. But I think I really think, if we do as well as we think we are, where you’ve got a placebo group that’s racing to really quite significant cognitive impairment. And the XPro group, which is relatively stable, I don’t think they’re going to force us to treat patients on placebo for a very long time, but they’re going to want to see more patients.
200 patients will not be the size of the next trial. It will be at least double that, probably three times that, my prediction.
Jason McCarthy: So, from — in the placebo group, even with acetylcholinesterase inhibitors or something like that, how far out can they go even with a true placebo effect, and then start to decline kind of like not to fake it till you make it, but you know what I mean, where that they will eventually…
Dr. RJ Tesi: Yes. So, two points. You see the acetylcholinesterase inhibitors, in general after three months, certainly after six months, you don’t see any benefits with those drugs. Patients have to be on a stable therapy before they can be enrolled and that’s for three months. So, any patient that would be enrolled with acetylcholinesterase inhibitor in that result for instance, would have been on the drug long enough that they are no longer benefiting from the drug. But as you know, many patients are on the drugs and it’s really the doctors are treating themselves as much as they’re treating the patients at least that’s my clinical view. I think that the early question asked by the Tom Shrader’s group was regarding anti-amyloid is interesting.
I don’t think the monotherapy trial will not — patients won’t be on maintenance anti-amyloid. That will be a separate trial and a separate question that we’ll ask hopefully with a partner that has an anti-amyloid drug because they’re the ones who I think will be the most curious, if the addition of combination therapy may improve both the safety profile of those drugs and the efficacy profile. But that’s the question of the future. And the first thing we need to do is prove that the combination of safe and animal models. And as I mentioned, those studies are underway.
Jason McCarthy: Just one quick question on INKmune. I think I heard earlier the potential to move towards renal cancer next, depending on resources, of course. But is the selection of renal cancer have similarities to prostate cancer choice in terms of there seems to be a higher proportion of NK cells versus T cells in those tumor types?
Dr. Mark Lowdell: Absolutely. So, there’s a long history. I mean, last week, I was examining a PhD student at the Karolinska who spent four years, looking at the same issue. And yes, renal cell cancers are typically heavily infiltrated with NK cells. And there’s a prognostic benefit to those patients who have a high NK cell infiltrate. And in fact, there’s a negative prognostic effect of having a high CD8 T cell infiltrate. And of course, the drugs that have been approved for renal cell cancer have been NK targeting often failed in IL-2. So, yes, that’s really the rationale behind that, and we’ve got some very nice data just to demonstrate that NK cells do target renal cell carcinoma cell lines better after they’ve been primed to INKmune.
Operator: Our last question will come from Daniel Carlson with Tailwinds Research.
Daniel Carlson: RJ, just you talk about hopefully showing flat on cognition as opposed to steep decline in the placebo group. I’m wondering if you do put up those type of numbers, is there any chance that conditional approval post to Phase II?
Dr. RJ Tesi: Yes. Right. Your lips to god’s ears. I do, as much as the FDA has tortured us, I do believe, in general, the FDA has their heart in the right place. And if the results are extraordinary, and I would consider that an extraordinary result, not only will investors be excited, not only will the Company be excited, but the FDA gets excited. And who knows what will happen, Dan? They will do, they will pull out all the stops to help push us along. I don’t know what that looks like, but they get excited about groundbreaking data just like you and I do. So, is there a chance? Yes. Would I bet more than a steak dinner on it? At this point, no. But, man, if we knock it out of the park, I think all bets are off. We’ll just have to see what they say.
As you know, patient, advocacy groups make a big difference with the FDA. The Alzheimer’s field or the Alzheimer’s advocacy groups, although there are a lot of patients, are not particularly vocal compared to some of the other indications, which are smaller such as ALS and DMD. I don’t know. It’s a great question. I like to dream about it, but I’m not going to hold my breath, Dan.
Daniel Carlson: And just sort of a follow-up on that. What about other jurisdictions? Are they all going to fall in line behind the FDA or might it get approved on those results elsewhere?
