Supernus Pharmaceuticals Inc to Review Open-Label Phase 2a Study of SPN-820 for the Treatment of Major Depressive Disorder Call Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Andrew Tsai - Jefferies - Analyst : Hi. Thanks. Good afternoon. Congrats on the data. Thanks for taking my questions. With this MDD data on hand, how do you feel about the ongoing TRD study results? Would you expect efficacy to look stronger since that study, I believe, is dosed daily, not in a pulsatile manner? What would that mean for safety as well? Secondly, this was a 10-day study. It's still fairly short, big picture. What gives you the confidence we'll continue to see durability over time in that five-week TRD study and not see tachyphylaxis over time? Thanks. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Andrew Tsai - Jefferies - Analyst : Thank you. The last question is, on the cognitive disorder, can you confirm if those rates were mild and moderate in nature, not severe? Can you give us a frame of reference what other drugs show on the rates of cognitive disorder? Thank you. Jonathan Rubin - Supernus Pharmaceuticals Inc - Senior Vice President, Chief Medical Officer - Research and Development Yeah. There were no severe events in the study. I don't recall if they were mild or moderate. I can look that up. Cognitive disorder is something that is associated with depression. It's not surprising that we saw this, saw cognitive problems. We'll have to see in the placebo-controlled study, do we see it equally in drug and placebo, or is there a difference? If you look at other studies, you're probably going to see that as well.

Question: Stacy Ku - TD Cohen - Analyst : Thanks so much for taking our questions, and congratulations on the data. Just first, based on these results, can you talk about your plans for SPN-820 and MDD specifically? How do you anticipate this being used? And then, is it possible to disclose any other metrics, maybe the percentage of patients that might have achieved remission by HAM-D6, or the number of patients that achieved 50% reduction of HAM-D6, maybe any of these endpoints from address? That would be appreciated as we're trying to parse through the data. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Stacy Ku - TD Cohen - Analyst : Okay. Very helpful. Thank you.

Question: David Amsellem - Piper Sandler - Analyst : Hey, thanks. A couple for me. Sorry if I missed you addressing this earlier on, but I wanted to get your thoughts on what to make of the rate of somnolence and dizziness. I guess the question here is, are there significant sedating properties here that we need to be mindful of? How do you think about that, both clinically and even commercially, to the extent that it gets that far? So that's number one. Number two is, so this is a study in MDD. You've got the Phase 2b in treatment-resistant depression. I guess the question here is, as you're thinking broadly about the development program, are you looking at this more in a sort of TRD population with suicidality or more broadly in MDD? And help us better understand, at least given what we know now, how you're generally thinking about the various depressive subgroups. Thanks.

Question: David Amsellem - Piper Sandler - Analyst : Okay, thank you.

Question: Annabel Samimy - Stifel Financial Corp - Analyst : Hi, thanks for taking my question. Interesting data. I'm curious, the consistency between the HAM-D6 score and the MADRS were pretty similar. And I guess that's interesting given some of the inconsistencies we saw in Phase 1. So I'm just wondering, do you have any explanation for that? And just to give you increased comfort for the TRD study that's coming up. And then secondly, if you do continue to explore this in Phase 2, the dosing every three days is also pretty interesting. Do you think that you'd be exploring different dosing regimens in Phase 2, different dosage strengths, given the strong effect we already saw? Thanks.

Question: Annabel Samimy - Stifel Financial Corp - Analyst : Right. Well, what I'm curious about is given the, I mean, you saw some pretty good consistency between the two scores in this study and that's notable given the inconsistency seen in Phase 1. And given what we've seen in terms of the similarities of the spaces, I'd give you increased comfort moving into the GRD study and what that might mean for the GRD study. Jonathan Rubin - Supernus Pharmaceuticals Inc - Senior Vice President, Chief Medical Officer - Research and Development Okay. Got it. Yeah. So we did look at the data in comparison to the Phase 1b study conducted by Navitor that's been previously reported. In that study, there was a statistically significant effect on the HAM-D6 that was seen within a few hours. And there was just a mild to moderate effect on the MADRS. And in looking at those two studies, there's some several important differences. One, the 1b study had a single blind placebo lead-in. That design is actually somewhat controversial. There are pros and cons of doing it. But what is known is that when you do that, it reduces both the effect for the placebo arm as well as the effect in the active arm. In addition, that study was not an adjunctive study. That study was a monotherapy study. And the demographics of that study were a little bit different than the demographics in the open-label study that I'm reporting today that we're reporting. And notably, in the 1b study, it was mostly older males. And in this study, we're seeing younger females. The younger females in the baseline age of 40 is more representative of what we see in the depression world. And in the 1b study, I think there was some selection bias in terms of who they were evaluating at their centers in coming up with an older population of males. And I think predominantly, if you put all those three things together, that's why you were seeing some inconsistencies in the data. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Annabel Samimy - Stifel Financial Corp - Analyst : Thank you.