ACADIA Pharmaceuticals Inc at Needham Neuroscience Forum (Virtual) Transcript

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

Question: Ami Fadia - Needham & Company - Analyst : Okay. Thank you, Steve. That was a good overview. I'll probably be spending most of our time on the three key programs, as you mentioned. Maybe I'll start with the Rett syndrome study for trofinetide that was read out last year, and the company is going to submit the application. Can you talk about the endpoint that was studied in the trial in the Lavender study, and put in context for us what the change in RSBQ and the change in CGI score means from a clinical perspective?

Question: Ami Fadia - Needham & Company - Analyst : Got it. Yeah, that's helpful. Can you put in context for us the magnitude of change that we have seen in RSBQ as well as the CGI-I? And then the reason I ask is because I think the change in the RSBQ score was certainly several points, but the change in CGI-I was a [0.3] change. And I think we have received questions from investors around how does one evaluate what this really means in the day-to-day lives of patients from a clinical perspective? So, how should we put that into context?

Question: Ami Fadia - Needham & Company - Analyst : Got it. So, I guess to summarize what you're saying is that we saw meaningful changes in several components of RSBQ score, but the reason we didn't see maybe a larger change in CGI-I really has more to do with the course of the disease. And we can't expect these patients to start becoming independent, at least. And that's why it appears to be -- to have a more moderate impact on the CGI-I score. 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 16, 2022 / 7:20PM, ACAD.OQ - ACADIA Pharmaceuticals Inc at Needham Neuroscience Forum (Virtual)

Question: Ami Fadia - Needham & Company - Analyst : Yes, okay. That's very helpful. Thank you for putting that in context.

Question: Ami Fadia - Needham & Company - Analyst : The other question that we've been getting from investors is around the side effect profile. We saw some higher rates of diarrhea in patients that were taking trofinetide. Can you put in context for our listeners how much it really impacts their quality of life, what is the baseline condition that these patients face? And would they see this type of diarrhea as impacting their quality of life or not?

Question: Ami Fadia - Needham & Company - Analyst : Okay, all right.

Question: Ami Fadia - Needham & Company - Analyst : Okay, that's very helpful. I'd like to move to the topic of pimavanserin in ADP. You announced the AdCom that we should expect. Perhaps if you could give us some -- any early thoughts around the timing of the AdCom and, if at all, if there's been any communication with the FDA. I think it's obvious what the content would be, but if there's any additional communication with the FDA around what to expect of the AdCom that would be helpful to know?

Question: Ami Fadia - Needham & Company - Analyst : Okay. I guess I wanted to just dig into two aspects and greatly around the -019 Study for a conversation. You've provided us with a lot of color around some of the additional analysis that you submitted to the FDA. I want to just go back to two things. Firstly, in the complete response letter from the FDA, I believe that there was an issue that was highlighted by the FDA with regards to having no type I error control for secondary endpoints because of a single center in the study. Can you explain why it is necessary to have multiple sites when you design a clinical trial? And in this case, what was your approach taken to address this question from the FDA? 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 16, 2022 / 7:20PM, ACAD.OQ - ACADIA Pharmaceuticals Inc at Needham Neuroscience Forum (Virtual)

Question: Ami Fadia - Needham & Company - Analyst : Got it. So, I'm confused, what was the issue or what was the concern the FDA raised?

Question: Ami Fadia - Needham & Company - Analyst : Got it. So, perhaps the protocol deviations may be more central to what they were -- they had raised in their letter. So, can you talk through that?

Question: Ami Fadia - Needham & Company - Analyst : Got it. Well, this was actually very helpful. Have you -- did you get a chance to discuss this in some of your meetings with the FDA prior to the resubmission in much detail?

Question: Ami Fadia - Needham & Company - Analyst : Yes. This was actually very helpful to hear. Thank you for that. Let's move on to pimavanserin and negative symptoms of schizophrenia. This is an indication where there's really not much that's available in the market, available to patients today, and huge and [really] some interesting data in the Phase 2 advanced study in negative symptoms, where we saw an improvement of 3 points in NSA-16 score. Can you help us understand what it means from a clinical perspective? How much of a change should be considered clinically meaningful just for context? 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 16, 2022 / 7:20PM, ACAD.OQ - ACADIA Pharmaceuticals Inc at Needham Neuroscience Forum (Virtual)

Question: Ami Fadia - Needham & Company - Analyst : Got it, okay.

Question: Ami Fadia - Needham & Company - Analyst : Yes, yes. No, that's helpful. Thank you for putting that in context. I wanted to understand -- so there were some details, if you look at different subgroups.

Question: Ami Fadia - Needham & Company - Analyst : And then I'll just maybe read out a couple of things.

Question: Ami Fadia - Needham & Company - Analyst : And maybe you can tell us which one should we be focused on.

Question: Ami Fadia - Needham & Company - Analyst : So, we saw greater improvement in NSA--16 when the patient's baseline CGI score was greater than 5. Patients with more than five years of schizophrenia appear to have benefited more. Male patients seem to have benefited more. And then I think the topic of most interest to me is that you saw better results in subgroup of patients out of Europe and (technical difficulty) the US sites. So, can you help us with some of these things into context?

Question: Ami Fadia - Needham & Company - Analyst : Yes, so that's correlated. 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 16, 2022 / 7:20PM, ACAD.OQ - ACADIA Pharmaceuticals Inc at Needham Neuroscience Forum (Virtual)

Question: Ami Fadia - Needham & Company - Analyst : Got it. So, from an FDA perspective, an ADVANCE 2 conducted ex-US will be perfectly acceptable for a filing package?

Question: Ami Fadia - Needham & Company - Analyst : Got it. I've been told that we have ran out of time, but I want to squeeze in one or two quick questions.

Question: Ami Fadia - Needham & Company - Analyst : Just in terms of the ADVANCE 2 study, if I think about the dose titration in the ADVANCE 1 study up to 34-milligram dose, now you're studying only 34 milligram. Are there any implications that I should be thinking about in terms of either side effect profile or discontinuation rates I should be thinking -- expecting in ADVANCE 2?

Question: Ami Fadia - Needham & Company - Analyst : Got it. And last question from me, in terms of harboring for the study at the 34-milligram dose, how have you powered the study and is it powered to show a 3-point change in NSA--16?

Question: Ami Fadia - Needham & Company - Analyst : Okay, all right. I think it's time for me to close the session. Thank you so much for -- both of you for your time. This was a very productive discussion and hopefully the audience felt the same. Thank you so much.

Question: Ami Fadia - Needham & Company - Analyst : Thanks. Bye-bye. Have a good day.