Praxis Precision Medicines Inc at Cowen Health Care Conference (Virtual) Transcript

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

Question: Ritu Baral - Cowen and Company, LLC - Analyst : We are going to start with some neuropsychiatry thematic questions, questions that span all -- multiple, if not all of the companies, and then we'll go to sort of mini fireside chats for the individual companies with the time that we have remaining. We are going to start with the bogeyman of all depression studies, really all neuropsychiatry studies' placebo effect. You all have neuropsychiatry, either PTSD or depression studies underway where you are going to be looking at placebo. Why do these rates keep rising? Is it anticipation? Is it just conduct patient selection? And what can be best done to manage them? What are your programs doing to minimize the effect and keep it under control? Because obviously, it can compound power in the worst possible way.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : So what you're saying is that conduct quality has actually declined, not that it stayed the same and placebo's going up?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Rolando, is there anything that you're doing -- oh. Andy, we'll get to you in just a second. But as far as your -- Rolando, as far as the A-type platform of programs, is there anything that you're sort of consistently doing across your depression studies and even into other studies including anxiety, including substance abuse that you're doing to control placebo?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. Andy, go ahead. And also, if you can address what Aptinyx is doing because it's not like pain studies are protected from placebo effect either. And if you could just spend 10 seconds just reviewing the pain program that you have, the two trials that will be up very shortly too. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 07, 2022 / 2:10PM, PRAX.OQ - Praxis Precision Medicines Inc at Cowen Health Care Conference (Virtual)

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Guy, go ahead.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : The next thematic point I want to discuss and we will actually be discussing this with our KOL panel, which would be Wednesday morning, I hope everybody can tune in for that, but it's this idea of durability of effect for a new generation of neuropsychiatry drugs across various mechanisms that may be administered in episodic fashion. And as I look across our Brady Bunch screen here, Theis, that's you with GH; COMPASS, Guy; or Rolando, you've got approaches like that with atai; whereas Marcio, you're taking a more chronic approach to MDD with your GABAergic agent, and that's the PTSD approach as well that Aptinyx is taking. Let's start with the idea of endpoints to prove durable effect. What are the most important endpoints? We will ask the KOLs this on Wednesday. But is it just statistically significant separation at time point x, time point y? And how do things like durable remission, durable response play into what's generated that's useful to the KOLs? Guy, let's start with you this time.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Guy, so you reported nothing but remissions in your data. Can you talk about the time points? They're most important as you take your (multiple speakers)

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Marcio, you brought a good point up about safety. All of your drugs will have a differential safety profile from standard of care, which I think no matter what program we're talking about, it's SSRIs. How is the agency looking at the safety profile of new mechanisms in general? Are they default worried about suicidality no matter if you have an NMDA drug, no matter if you have a GABA drug, no matter if you have a 5-HT2A drug like the psychedelics. Are there any specific issues to GABA? Are there specific issues to NMDA? Are there specific issues to the psychedelics? Yeah.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. Let's move on briefly before we get to the individual company questions. I want to ask about Europe. This hasn't come up a whole lot in my conversations with really any of you. US has been the focus. How do European regulators approach approval for certain new mechanism neuropsychiatric drugs? Is it similar to the FDA? Are there review, like EMA, I think it's MHRS now, considerations that are different from FDA considerations? And then, gosh, getting anything paid for in Europe is hard. Any first thoughts on how country-by-country reimbursement actually sees the unmet need in depression and PTSD?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : So if we just focus on the US, coming out with a branded price range drug in a field dominated by SSRIs, from a US perspective, how are you going to communicate the value proposition to the private payers? Maybe Marcio, we'll start with you because if you can sell [trends alarm], you can sell anything. Sorry.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. Theis, go ahead.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. Well, let's move now actually into the company-specific discussions. Andy, we'll start with you and Aptinyx. And actually, this will probably go to something that -- I think it was Marcio that mentioned this, but just the poor response for standard of care in PTSD, which of course, segues into the question of how would you position a better-branded drug versus cheap generics? Can you talk about the effectiveness, the real-world effectiveness of SSRIs in PTSD and segue into the scientific rationale behind your NMDA modulator, 783, in the condition?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Do you have a favorite dose between the 50 and 150, which are the two doses in your Phase 2 program? Should we expect a dose response? We almost never see one in neuropsychiatry, it seems.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : And do you think neuroplasticity will play into 783 and PTSD the same way that it kind of has for 2925 and DPN, just as far as the longer you've had the condition, the less likely you are -- the differential -- there's more likely to be differential response. And can you remind us when your PTSD data is coming?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Sounds good. Let's move to Rolando now and atai. Let's start with your -- I would say, the program that you have that's of highest investor interest, which is 101 R-ketamine for TRD. Can you speak to the company's strategy for clinical positioning of R-ketamine versus Spravato? What sort of clinical profile differential does the data in hand suggest that you will be able to achieve? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 07, 2022 / 2:10PM, PRAX.OQ - Praxis Precision Medicines Inc at Cowen Health Care Conference (Virtual)

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Other features of the clinical benefit? Or other repeat (multiple speakers)?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Okay. So what would good Phase 2a data look like from the trial? What are you hoping for?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. Got it. I want to move to actually a non-depression program of yours, this is 007, Cognitive Impairment Associated with Schizophrenia. You generated some really, really intriguing positive EEG biomarker data recently. And the main conversation that I've had with investors is how is what we're going to see on EEG going to translate into clinical data? And also what cognition measures are going to be utilized in this program going forward? I mean, cognition is just such a hot button issue all around and this is a new field, so there's a lot of discussion on what the forward program is going to look like in the structure.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. So we've covered 101, we've covered 007. This is not a favorite child question, but with 11-plus programs, what are the two that you think investors should be focused on for the next year, beyond those two?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. That's very helpful. Thank you, Rolando. So let's move on to Guy and COMPASS. Congratulations on your data last fall in your Phase 2b study. Can you talk about the data that you generated, tying in the original part of the conversation that we had on durability. Can you just review remission REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 07, 2022 / 2:10PM, PRAX.OQ - Praxis Precision Medicines Inc at Cowen Health Care Conference (Virtual) response data generated out of the Phase 2b, and what sort of follow-up are you doing on these patients? And then we'll get to your planned Phase 3.

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Is there any aspect to sort of activities of daily living? Especially as you think about the TRD population where that could really be impaired versus mild-to-moderate MDD, where it's more difficult to see impaired activities of daily living. Is that an aspect of how you might see a differential response worth paying for that might be teased out in the Phase 3?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : What have you guys set on timelines for this FDA meeting and when the Phase 3 might kick off? Or at least what's almost more important is when you can publicly discuss the final details of the Phase 3 protocol. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 07, 2022 / 2:10PM, PRAX.OQ - Praxis Precision Medicines Inc at Cowen Health Care Conference (Virtual)

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. And as far as the control arm, are you thinking about sort of that 1 milligram subclinical dose for the Phase 3? Is that the intent?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Great. Theis, let's move to you. Congratulations on your December data, Phase 1/2. You're approaching this with a titration -- you're approaching TRD MDD with a titration angle, something that neuropsychiatrists are super familiar with, with psychosis, even SSRIs. Can you speak a little bit to the dose titration methodology that you're seeking around peak experience? And how do you think this will play in the real world? Do you expect that patients will find a dose upon first treatment and that's going to be their dose upon any potential relapse? Or is this something that will be -- potentially will be something that might need to change from episode to episode?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : So I know you guys have had less time than even Guy and COMPASS have, but how are you thinking about the next trial, the Phase 2b? How are you going to track further durability data than the Phase 1/2, and are you going to start investigating potentially redosing in that Phase 2b?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Great. Marcio, let's get to you. Praxis and your Aria data that you said is going to be in June. This is a Phase 2/3 trial, potentially registrational. You very helpfully went through key aspects of powering on your last call. But could you discuss what do you hope for at day 15, even beyond statistical significance? Maybe are there any expectations around secondary endpoints? Do you care about what you see at day four? I think you mentioned that was the first assessment, it's remote. Insofar as positioning versus other GABA agents, how should we think about day 4 and 30 versus just the primary endpoint at day 14?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : And how should we think about sedation and somnolence? You're treating up to day 30, primary endpoint at day 15. Do you expect that the rates for sedation and somnolence will be different at day 15 and day 30? Could they be higher at day 30? Could they be lower at day 30? And just generally, what's the range that you're expecting to see in both of those?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : That's next-morning somnolence?

Question: Ritu Baral - Cowen and Company, LLC - Analyst :

Question: Ritu Baral - Cowen and Company, LLC - Analyst : And same at day 30 versus day 15? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 07, 2022 / 2:10PM, PRAX.OQ - Praxis Precision Medicines Inc at Cowen Health Care Conference (Virtual)

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. And then let's take 30 seconds, we're already two minutes over, but I do want to address the Acapella adjunct study, which is ongoing. And you mentioned on your earnings call that is not just adjunct but dose finding. Do you anticipate that there could be a lower dose found versus the monotherapy study? Or how do you see the interaction between GABA and SSRIs?

Question: Ritu Baral - Cowen and Company, LLC - Analyst : Got it. Well, great, everyone. We're a few minutes over. Thank you, everyone, for all of the answers, all of the insights into the broad questions, into your individual challenges and strengths, and look forward to the conversations. Thanks, everyone.