Randall Kaye: In our 102 data, we learned that there was good solid dose proportionality between the oral dose given, what appeared in the plasma and probably most importantly, what ended up in CSF. We compared the CSF dose concentrations that we observed relative to the KI or the dissociation constant. And what we found is that we were getting at or, in most cases, well above the KI at our top dose at 12 milligrams TID. And we also found that, even at 6 milligrams, which is the start of the titration, we’re getting great receptor engagement, somewhere around 70% or so of the KI. So what that tells us is, that means you can dose optimize, you can modify, you can adjust as we go into further clinical studies next year that we can go up and down based on the data that we’re seeing.
And that is the opposite of what you can do with Fintepla currently. At a point in time, as these patients go from young children to adolescents and older, as they gain weight, you will cap out. So you cannot continue to increase the level of fenfluramine in order to match the increasing weight. You just can’t dose optimize the drug that has a restrictive REMS.
Kevin Lind: On the second question, the BID formulation, again, we are focused on making sure we have that BID for the Phase 3. There’s some intellectual property involved in that, that we’re not ready to disclose at this point and work through, but we remain on track for BID for the Phase 3.
Operator: And our last question comes from the line of Patrick Trucchio from H.C. Wainwright.
Patrick Trucchio: I’m wondering, first, if you can tell us if there’s any evidence that the 5-HT2C mechanism could be complementary or synergistic with that of cannabidiol? And would you expect a portion of patients enrolled in PACIFIC to be on cannabidiol background treatment? And if so, what portion of those patients?
Randall Kaye: I probably should have discussed them earlier. So we do allow patients to have background of cannabidiol of Epidiolex as long as they’ve been on a stable dose. I don’t have specific numbers for you. It’s hard to say whether they’ll be synergistic. I’d like to describe it somewhat differently. When you think about these complicated patients with these developmental and epileptic encephalopathies, multiple modality treatment with the right medication is going to make sense. So I can see a time €“ I’ll kind of refer to this as precision and targeted treatment of patients where the clinician is going to the shelf and saying I want to have the best, safest, efficacious cannabidiol. And I think they’re also going to be reaching up to that shelf in the DEE space for the most efficacious and safest 5-HT2C. So I can’t say whether they’d be synergistic, but they certainly €“ one would expect them to be to be complementary.
Patrick Trucchio: How big of a concern is that Fintepla blackbox on adoption among clinicians and patients and what would need to be demonstrated in LP352 program to avoid having a similar blackbox warning on the label?
Randall Kaye: I wouldn’t expect to have a blackbox warning. We’ve had the discussion with the agency. Our compound does not interact with the 5-HT2B receptor. So a priori, there’s no expectation to do the kind of work that was required with some Fintepla. So, we asked the FDA specifically about conducting echocardiograms, they’re not required by this program, and we wouldn’t anticipate that that would be part of it. To answer your question more clinically, what I’m hearing from other clinicians, these are really complicated patients. And they’re very, very fragile. Adding on the component of an echocardiogram, getting it scheduled, it’s not like it’s right down the hall in these clinics. It could be in another building. These are not the most mobile of patients.