So the next topic I’d like to talk about is the review of the results from the Phase IIb study of neflamapimod in the treatment of mild dementia with Lewy bodies. So dementia with Lewy bodies, at least in the United States, has no FDA-approved treatments, and that’s also true in the European Union and the UK. So everything that we’re doing is treating currently is more or less off-label...
So the next topic I’d like to talk about is the review of the results from the Phase IIb study of neflamapimod in the treatment of mild dementia with Lewy bodies. So dementia with Lewy bodies, at least in the United States, has no FDA-approved treatments, and that’s also true in the European Union and the UK. So everything that we’re doing is treating currently is more or less off-label. So there’s a real unmet need to find therapeutics that would be effective in people that are living with dementia with Lewy bodies, which is the second most common cause of degenerative dementias in older adults. So this study was a Phase II study comparing neflamapimod 40 milligrams three times a day against a placebo. And so there were two things, two parts of the study planned. There was the randomized double-blind placebo-controlled study, which was a 32-week study, and then a 48-week open-label extension. Real quick, the upshot of the randomized double-blind placebo-controlled study, it was that we didn’t see any effect of the drug. So that was a negative study. But the open-label extension was ongoing as we were reading out the double-blind phase of the study. So that was very disappointing. But we kind of then, when you have a study that’s negative, you can learn a lot about what’s going on. So we dove a little bit more into this. And it turns out that the people in the treatment arm did not reach sufficient plasma levels. So they were basically below the plasma level that’s known to be effective for the treatment with neflamapimod. Diving into a little bit more, there was a batch of medication which was getting toward the end of its life. And so let’s call that batch A. And so everybody in the randomized double-blind placebo-controlled trial was either in a placebo or batch A, which effectively acted like a placebo. But for the open-label extension, this was already pre-planned. A new batch of medication was created. Let’s call that batch B. And so in the open-label extension, there was actually a planned titration curve where some people got batch A for the entire open-label extension. Some people got batch B for the entire label nor the investigator knew what batch they were on. Placebo-controlled because batch A acted like a placebo and batch B acted like active drug study. Now, it wasn’t randomized, but other than that, it had all the exact parameters that you would see in a clinical trial. And in this case, the batch B reached plasma blood levels that were necessary for a treatment effect, and it met its primary outcome and most of its secondary outcomes. So this was very exciting. So even though it was not the way it was originally designed, it allowed us to actually test the importance of getting effective plasma blood levels, right? So that we could see a treatment effect. And when we saw a treatment effect, then the people met their primary outcome of the CDR or clinical dementia rating, some of boxes, as well as a bunch of the secondary outcomes. Also, as part of the screening process, people were screened for concomitant Alzheimer’s disease with a pTau181 blood-based biomarker. And we used the Quanterix Simoa system. And the initial levels that were proposed, because Quanterix had changed their assay, was at 27 picograms per milliliter. But we found that actually a 21 level was a better level to use. And for those people, when we stratified by below or above 21, those people less than 21 picograms per milliliter had an enhanced effect. So not only did we demonstrate in the open-label extension, the effect of neflamapimod reaching its primary outcomes is that that primary outcome effect was enriched in those people who did not have lots of concomitant Alzheimer’s disease. So knowing all this, this allowed us then go to the FDA to describe our Phase III plan, which was agreed upon. And so the plan now is to hopefully open up the Phase III study sometime in the latter part of 2026. And this would be a great unmet need for the 1 million or so Americans who are living with dementia with Lewy bodies for which there’s no approved therapies.
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