LB Pharmaceuticals Inc Common Stock TD Cowen 6th Annual Novel Mechanisms in Neuropsychiatry Summit

Thank you so much for having us. Really happy to be here.

LB-102, as you mentioned, is a derivative of amisulpride. Amisulpride is a generic antipsychotic that has been approved around the world but was never approved in the U.S. LB-102 is a very selective inhibitor of D2, D3, and 5-HT7, and really very little else. So it has very few off-target effects. Amisulpride is a drug that has very poor permeability into the brain, and so one of the improvements made with LB-102 was to improve the efficiency in crossing the brain. As a result, LB-102 is a much more potent molecule than amisulpride. It also is enabled for once-daily dosing. So it's a very selective inhibitor of D2, D3, 5-HT7, and it's once-daily dosing.

Yeah. D2 is obviously very important when it comes to suppressing dopamine release, which is really mechanistically what you need to do to treat psychosis-related indications like schizophrenia. D3 and 5-HT7 have been implicated as both pro-cognitive as well as antidepressant. So those two receptors are mechanistically part of the reason we believe that we'll be efficacious in the mood disorders like bipolar depression, and adjunctive MDD. There's another mechanistic reason for success in both psychosis and MDD, and that is that LB-102 is a benzamide, like amisulpride, and there's an interesting bimodal mechanistic activity with this molecule, and that is at high doses, it operates to suppress dopamine, and at low doses, it actually triggers the release of dopamine.

You see this in the way that amisulpride is used and the way that we intend to use LB-102, which is at the highest doses, you're treating schizophrenia and other psychosis type of indications, and then at the lowest dose, you're treating depression-related indications. So for LB-102, we're intending to treat schizophrenia at 50 to 100 milligrams. That's what we're studying in our phase III trial. In the adjunctive MDD indication, we're actually looking to study it at 15 to 25 milligrams.

Yeah. It was originally developed by a very small biotech company in France called Synthélabo, and it was first approved in France in the late 1980s. Sanofi bought Synthélabo in the late 1990s, and at that point, they tried to bring amisulpride to the United States. FDA asked for a full development program, and that just wasn't compatible with the patent life that remained in the U.S. Of course, this was at a time when antipsychotics weren't necessarily blockbusters at that point in time. So the decision was made to not bring it to the United States. Amisulpride is actually considered one of the most efficacious antipsychotics. It has a treatment effect of about 0.73, which is second only to clozapine. It also is considered one of the more safe and efficacious antipsychotics with one of the lowest all-cause discontinuation rates among the antipsychotics.

And it's one of the few that has been studied in patients with predominantly negative symptoms. In three separate placebo-controlled trials, it was demonstrated to be statistically significantly better than placebo in treating patients with predominantly negative symptoms. So it's viewed pretty widely as a very efficacious drug with a nice balance of safety and tolerability.

That's right. We're able to accomplish what we hope, and what LB-102 is designed to do is to accomplish, and be as efficacious with a much lower dose.

What we determined was that 50 milligrams of LB-102 is about the same as 400 milligrams of amisulpride. So it's a much more potent molecule.