Rapport Therapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Sure. Well, Imogen, thank you so much for having us. Rapport Therapeutics is a company that is focused on precision neuroscience. We believe that although precision is a loosely used term sometimes in our industry and in neuroscience, we actually can bring that to life. We believe that based on our scientific foundation, which is receptor-associated proteins. The best way to think about receptor-associated proteins is through the lens of our lead program, RAP-219. RAP-219 is a TARP gamma-8 AMPA modulator. TARP gamma-8 is the receptor-associated protein or a member of a family of receptor-associated proteins associated with the AMPA receptor. And what it allows is with a small molecule to have a level of specificity that really hasn't been seen historically in neuroscience. This is a program where we released really unprecedented phase II results in September of last year in focal onset seizures.

We see it as an opportunity for a pipeline and a product, and we're coming up on the release of our bipolar data in the fourth quarter of this year in October. We also have plans to further extend this program with the formulation of a long-acting injectable. In addition to that, we have a fully integrated discovery pipeline that we believe gives the company an opportunity to really have a self-sustaining and regenerative pipeline. And we really bring that scientific foundation of receptor-associated proteins all the way through to our discovery pipeline as well.

Yeah. I actually think if you look at it from a stock perspective, investors are looking at Rapport like a late phase II focal onset seizure, start of phase III focal onset seizure company. If you look at our comps, you look at the market potential. I would say they're cautiously evaluating the potential in bipolar mania, which is, I think, where they should be looking at it. I don't think we have any really credit yet for the long-acting injectable, which according to our market research, could double the size of the opportunity in FOS as we move that forward. I think they're appropriately focused on the potential with the bipolar mania, but really grounding in the FOS.

Sure. Admittedly, a neuropsych indication has less translatability preclinical to clinical, as, say, a neurology indication such as focal onset seizures. We knew that as we developed a strategy for our lead program and went into bipolar mania. There's also some real reasons to believe in this approach in bipolar mania. First is what we understand about the disease, and it is pretty well documented that one of the drivers in bipolar mania is excessive glutamate. What we know about RAP-219 is we are having an impact on glutamate through the modulation of the AMPA receptor via TARP gamma-8. The second is where that excessive glutamate is occurring kind of neuroanatomically, and what we understand and what the literature would say is that that is happening in the corticolimbic network. That exactly overlaps with the expression of TARP gamma-8 as well.

Then the third aspect is clinical precedence, and what we know is the anti-seizure medications that are used in this space, as well as another mainstay of therapy, which is lithium. Although those are somewhat dirty drugs that are having impacts across many different pathways, one of the common pathways is their impact indirectly or directly on glutamate, as well as AMPA receptors. So that was kind of the pieces of information we pulled together to really say, "You know what?

This is worth the investment and the experiment for a bipolar mania trial. We obviously took a lot of insight from what we gained in our focal onset seizure trial in terms of receptor occupancy, target engagement, and that has definitely increased our belief that at least going into this trial, we know that we have a dose that gets to therapeutic concentrations, that it's associated with the right receptor occupancy. At the end of the day, with all neuropsych trials, it comes down to how well can you execute these trials in a quality manner.

Yep. So you're right. There's really three labeled indications in bipolar disease. First is acute mania, second is maintenance, and then third is depression. The reason we went into mania is, one, we believe that based on the structure that I walked through in the previous question, that this was the right indication to step into first. The reality in clinical practice, although maintenance is a labeled indication, in clinical practice, if a drug is effective as well as tolerated in a manic episode, clinical practice would tell you that patients should stay on that therapy. So although maintenance is a labeled indication, we don't necessarily believe that it needs to be a labeled indication to drive utilization and maintenance. With that said, we will assess maintenance based on if we had positive data in bipolar mania. Bipolar depression is another area that based on the data, we will assess.

Very different pole than mania, and also different considerations as you think about enrolling and executing those trials, but that's something that we will investigate. Mania on its own is a multibillion-dollar market opportunity. So we believe with positive data in mania as well as positive registrational studies and thinking forward to potential market opportunity there, that is an opportunity that somewhat matches the market opportunity that we see in focal onset seizures.