ACADIA Pharmaceuticals Inc. (ACAD) Earnings Call Transcript & Summary

Welcome, everyone, to the 41st Annual JPMorgan Healthcare Conference. My name is Tess Romero. I'm one of the biotech analysts here at JPMorgan. I'm joined by Taylor Hanley and [indiscernible] from the team. Our next presenting company is ACADIA. And speaking on behalf of the company, we have CEO, Steve Davis. Before I turn it over to Steve, I just wanted to highlight that we do have a Q&A session after this formal presentation. There's an Ask A Question button in the portal for those that would like to submit in a question or we will have mic runners to take live questions as well. So with that, I'm going to hand it over to Steve.

Great. Thanks so much, Tessa, and thanks to each of you for weathering the conditions getting over here, we had a little rise in the rain. So hopefully, you all made it over dry this morning, and thanks to each of you who are joining remotely. I need to start with the obligatory forward-looking statement, the business of drug commercialization and development is as a number of inherent risks. So please see our SEC filings for a description of those risks as they relate to our business. I'd like to start this morning with why we do what we do. What you see here are families of Rett Syndrome patients in Parkinson's. disease psychosis patients. They have disorders that effectively shrink their world. They're very significant debilitating and debilitating disorders in both cases. Our mission is to elevate life and to restore some of the constraints or the loss that they have to the constraints of their disease. So this morning, I'd like to start by recognizing the people that deserve our very best, and that is the patients that we serve. There are 4 strategic priorities that underlie our business. First is our franchise with NUPLAZID in Parkinson's disease psychosis. We've guided to 2022 revenues of $510 million to $520 million. We'll be announcing those revenues relatively shortly when we release fourth quarter earnings. That franchise has been cash flow positive and profitable since 2019. It's an important foundation for our company. What NUPLAZID represents is the first and only drug approved to treat Parkinson's disease psychosis. So I go into greater detail in that in a few minutes. Our second priority is preparing for the launch of our second drug, trofinetide for Rett Syndrome. We completed a successful Phase III program and have filed a new drug application with the FDA. Our PDUFA date is March 12 this year. It's coming up very shortly. And here too, trofinetide represents if we're successful, the first approved drugs to specifically to treat the core symptoms of Rett Syndrome. Third priority is negative symptoms of Schizophrenia. We have completed a positive pivotal study our ADVANCE-1 study in this disorder. We have a second pivotal study ongoing, our ADVANCE II study. We should complete enrollment in the ADVANCE II study around the middle of this year. This is a 6-month treatment period, so we could have results in a little over a year from now. And then the first -- the fourth priority on this slide is Alzheimer's disease psychosis, where we're continuing to invest in a very significant unmet need, both in Parkinson's disease psychosis prior to the approval of NUPLAZID and in Alzheimer's disease psychosis today, all of the antipsychotics on the market are not indicated for use. They're not approved for use in these disorders. NUPLAZID is the only antipsychotic approved to treat Parkinson's disease psychosis. And we're continuing to invest significantly in trying to provide relief for the patients with Alzheimer's disease psychosis. Our lead candidate here is ACP 204. We're nearing the end of Phase I work. We should complete that work around the middle of this year, and then we'll move quickly into studies in Alzheimer's disease psychosis patients. Just one final footnote before I go to the next slide. We have a very strong balance sheet. We are approaching cash flow positivity. We do not need to go back to the capital markets to raise additional capital with the 1 caveat, of course, being if we do significant business development above and beyond what we've done historically then that could require that would be a very good reason to do it. So we're in a very good position in a very turbulent capital market today. This slide represents our broader portfolio in addition to the 4 priority programs I mentioned a second ago, we have an important and burgeoning early portfolio, both disclosed and undisclosed programs, highlighted by our SYNGAP-1 program. We have a second Rett Syndrome program at an early stage and a number of other programs that we're continuing to pursue, and we're very excited about not only the later-stage programs that I'll go into greater detail today, but also our early-stage portfolio. I'm going to shift now to focus on NUPLAZID in Parkinson's disease psychosis. I mentioned that we'll achieve over $500 million in annual sales in 2022. And I noted that NUPLAZID has been cash flow positive and in addition, increasingly profitable since 2019. This population has been significantly impacted by the pandemic. So Parkinson's disease patients obviously have very compromised medical condition, they're elderly patients. And Parkinson's disease psychosis typically occurs in the last 4 to 5 years of life of these patients. So we've lost a lot of these patients in the early days of the pandemic. So the market is just simply smaller. The population is smaller. A lot of these patients die. We've continued to gain market share in a smaller market. And the 2 principal headwinds that's impacted our business and maybe more importantly, the Medicalcare of these patients are on the -- in the office-based setting, we're continuing to see, it's been very persistent throughout the course of the pandemic, patients seeing their physicians in person about 80% -- 75% to 80% of the rate at which they saw their physician in-person part of the pandemic. When physicians are not seeing their patients in person in this population and for this condition, they're very reticent to prescribe new drugs. So it's impacted our new patient starts in the office space setting. In the long-term care setting, which is about 25% of our business, the office-based setting is about 75%. In long-term care, the headwinds have manifested primarily in addition to just the loss of population due to mortality during the pandemic. There have been significant staffing shortages. We've seen reductions in occupancy rates, reductions in new admissions, et cetera. We're beginning to see that change. So in the long-term care setting, we're beginning to see those conditions improve. And we are beginning to see some growth in that portion of our business. We're not seeing those changes yet in the office-based setting. So if you sum all of that up, what we're projecting and expecting to see is steady volume in this disorder and in this -- and in our business, with 2 catalysts that could change that. One is just a change in improvement in the pandemic conditions. I don't think this will last forever. I don't think this is a frame shift and patients will just behave differently and doctors differently in the longer run. But today, the conditions continue to impact our business and most importantly, continuing to impact the Medicalcare of these patients. So that's one thing that can catalyze growth. The second is -- and I'll go into greater detail in the next slide, but there are 3 very important new papers that have been published just in the last 6 months that highlight the benefits of Pimavanserin relative to atypical antipsychotics that are -- although they're not approved for use in Parkinson's disease psychosis patients, they're many times used off-label. I'll get to that more in a minute. Sometimes we get questions around the Inflation Reduction Act and the impact on our business. I can sum it up really quickly. It will have a very modest impact on our business for the remainder of this decade. We'll see a net pricing benefit of approximately 3%, positive 3% in -- through the third quarter of 2023 -- sorry, skip the slide. I'll finish this up really quickly. And we'll get some short-term benefits due to being -- qualifying for small business treatment under the Act. We do not expect to be subject to Medicare pricing negotiation at least through the remainder of this decade. Let's go to the real-world evidence that I referred to earlier. 3 papers, 2 of them assessing is there a difference in mortality rates between in one case, Parkinson's patients. And in the other case, Parkinson's disease psychosis patients that are treated with NUPLAZID versus atypical antipsychotics. What we see in the upper left-hand corner here is in the first publication came out just about 6 months ago. paper by MOSHOLDER ET AL. They demonstrated in this real-world evidence study. So what I mean by that is they took the Medicare claims database. It's a massive database, and they probed it to look at patients treated with NUPLAZID versus atypical antipsychotics. You have all sorts of great information that comes from that in terms of hospitalization rates, mortality rates, long-term care admissions, et cetera. And what they saw here was a 23% lower mortality risk for NUPLAZID versus atypical antipsychotics. During just the first 6 months, it was 35% lower mortality risk. And that benefit was maintained all the way out to 360 days. That's statistically significant difference in mortality between patients to NUPLAZID versus those on atypical antipsychotics. Second paper by LAYTON ET AL, just published a little over a month ago, almost identical results, 22% lower mortality risk for patients taking NUPLAZID versus those taking atypical antipsychotics, hazard ratio of 0.78, first 180 days of treatment, 34% lower mortality risk, cumulative mortality at one year, 23% lower on NUPLAZID then atypical antipsychotics. I should, just for context, note that all antipsychotics have warnings in their label that say there's an association of higher risk of mortality in elderly demented patients that take these drugs versus those who don't. Our label and the warnings go further to say this drug is not approved for treatment of those patients. Our drug, NUPLAZID, is the only drug that has a carve-out that says that in the second statement, this drug is not approved to treat these patients unless they have psychosis associated with Parkinson's disease. This is very important information from a medical perspective. We're in the process of disseminating this information, making sure that we do our job to get it out into the medical community, and very eager to see it absorbed in the community. Third paper deals with Healthcare Utilization. So again, proving the Medicare claims database to assess patients treated with NUPLAZID versus other -- versus atypical antipsychotics, is there any difference in hospitalization rates, in ER visits, in the length of hospital services, et cetera. And what we see here again is statistically significant lower all-cause hospitalizations, ER visits, length of stay in hospitals for NUPLAZID versus atypical antipsychotics. This is obviously very important information from a medical perspective in terms of loved ones that are in long-term care facilities, but it's also important from a business perspective to these long-term care facilities because these rates of hospitalizations, ER visits, length of hospital stays, et cetera, all feed into their star ratings. And if you have a family member or a loved one that is in a long-term care facility, you're probably familiar with this. I do and I remember when my parents went into long-term care, us looking at the star ratings of various institutions to kind of get a sense, well, how has the Medicalcare at this facility differ from that one? So it has a real economic impact to these -- to the business of these facilities. And having the potential benefit of NUPLAZID having lower -- causing lower rates of these feed into their star ratings, something that every long-term care facility is very focused on. So again, 3 important papers that have come out just in the last 6 months. We're in the process of getting them into the hands of the medical community and helping them digest the information. Then to shift gears to trofinetide for Rett Syndrome. I need to start by saying this is an extraordinarily debilitating disorder. It affects mostly girls, the males typically die in utero. There are a few male patients, but it's mostly girls. And they develop normally for about the first 2 years of life. And then at about age 2, where they typically can walk and talk, they begin to deteriorate developmentally and they reach a point where they can't walk or talk typically. Almost all these patients are in wheelchairs their whole life. They usually lose the ability the to communicate verbally and many times nonverbally as well. It's a very, very heavy burden on the girls, of course, but also their entire families. They have other symptoms besides the developmental symptoms relating to -- many times, they have seizures. Many times, they have respiratory issues. And for those kinds of noncore symptoms, there are drugs to treat those symptoms. We have antiseizure medications. We have drugs that benefit respiratory activity. There is no drug approved to treat the neurodevelopmental, the core symptoms of this disorder. There are about 6,000 to 9,000 Rett patients in the United States, so it's a rare disease. There are approximately 4,500 patients that have been diagnosed and are being treated today, again, not treated for the core symptoms because there's nothing to treat it, but treated for the other symptoms that they have. And I'm sorry, just one other footnote in terms of this being a neurodevelopmental disorder. That's important because if it were a neurodegenerative disorder, if the neurons were actually dying -- then in many neuro, particularly rare neuro diseases do have that characteristic, then you would have to catch the patients very early in order to -- because once the neurons have died, they're gone. But the neurons are still alive in these patients. They've just lost the ability to communicate or the ability to communicate across the synapse that space between neurons has been significantly degraded, leading to a whole array of symptoms across all of their developmental capabilities. Trofinetide is thought to work. Many times, we don't know exactly how drugs work even a lot of the very common drugs that we all taken are familiar with. We don't know exactly how they work, but it's thought to work by increasing the synaptic communication and by also being a neuro anti-inflammatory, having a neuro anti-inflammatory effect. So when we tested this drug in Phase III, we were eager to see just have a positive benefit. It had a benefit in Phase II studies. But we're also eager to see, well, what kind of benefit does it have? What we see on the left-hand side here in the Rett Syndrome Behavioural Questionnaire, is statistically significant benefit on trofinetide with a Two-sided p-value of 0.0175, an effect size of 0.37. Importantly, there are 8 domains in the Rett Syndrome Behavioural Questionnaire, Again, they relate to the broad array of symptoms that these patients have. And we saw a positive movement across all 8 domains. So that lines up with what we believe about the way the drug works. We believe we know that Rett Syndrome patients have a loss of synaptic communication throughout the ring. And we believe that trofinetide increases that synaptic communication and that then should produce benefits across their array of symptoms and what we saw in the studies indicates that it does. In this study, we did something that is not terribly uncommon, but it's always a higher challenge when you are developing a drug. We have 2 co-primary endpoints. So what that means is in order to have a successful study, you have to have statistically significant results across on both endpoints. So here the Rett Syndrome Behavioural Questionnaire is a caregiver assessment. On the right-hand side here, you see an investigator assessment, the clinical global impression of improvement scale. And here too, we see statistically significant results. So Two-sided p-value 0.0030 and an effect size of 0.47. So very unequivocal, efficacious benefits of the drug. Our key secondary endpoint is a scale that primarily is measuring communication ability and we also saw statistically significant results there with a strong effect size. On the basis of these results, we called a new drug application with the FDA. We -- our PDUFA date, as I mentioned earlier, is March 12, we're eager to get to the PDUFA day. And from all of the communication we have with the FDA, everything appears to be on track, and we're looking forward to getting there. I mentioned earlier that we're making significant investments in preparing for the successful launch in Rett Syndrome. I can sum these up in really 3 buckets. First is driving disease state awareness and education. So obviously, if you're a physician that's treating Rett patient, you know what Rett Syndrome is, if you're parents of a Rett Syndrome patient, you know what it is. But because of the broad array of symptoms, sometimes physicians and caregivers are not tuned into all of the various elements of the disease. And so an important part of the foundation we're laying now in the disease education work we're doing, and we'll continue to invest heavily in post launch is fine-tuning the awareness of these symptoms so that physicians and patients are better -- excuse me, and caregivers are better equipped to recognize benefits of the drug. So that's an important element of what we're doing on both the efficacy side as well as tolerability. So we're doing some very important work laying the foundation there. It's always important prior to launch of the drug, but particularly in a rare disease where patients have a broad array of symptoms, it's a very, very important exercise for us. Second is we've hired a very seasoned leadership team with significant experience in rare disease. I mentioned earlier, there are about 4,500 Rett patients diagnosed in the U.S. Many times, when you launch a new rare disease drug, the first order of business is can you find the patients because it's rare, patients don't pop up with every neurologist. And so in this case, we have the benefit of having a patient advocacy -- 2 patient advocacy organizations that are very, very active and have done an excellent job of identifying patients. In one case, their membership list runs into the thousands of patients. And so I think we'll have the benefit of having a relatively identifiable population right from the beginning. These Rett patients tend to be treated in 3 different settings. About 1/4 of the patients are treated in centers of excellence. There are currently 22 centers of excellence. There are a couple of more that are in the process of being designated by the patient advocacy organization that designates them. And so about 1/4 of the patients are treated there. A significant majority of the patients are treated at other hospital settings that are not designated as the center of excellence, but typically run academic centers, et cetera. And then a small group of patients are treated at stand-alone neurologist offices that are not associated with a hospital. Our launch plan includes plans to tackle all of these in an appropriate manner. I think the take-home message here is that it is a -- while this will be a separate sleeve, a separate dedicated sales force that we will have, it's not a vast -- we don't need a vast footprint to cover these territories, fairly concentrated. Third point is continue to leverage the strong support that we have in the Rett community. We're doing all the things you would expect us to be doing. We've established a hub. We have extensive resources that will be coming to bear to provide patients, caregivers, health care professionals with extensive support in transitioning from a disease that has no drug to treat it to one that does. So -- and everything that I've described in the slide is stood up, ready to go, we're eager to get to March 12. We're going to move to negative symptoms of Schizophrenia. So here, we're exploring with Pimavanserin, that's the generic name for NUPLAZID. The utility of Pimavanserin in treating the negative symptoms of Schizophrenia, let me just start a little bit of context here. So the negative symptoms, when we think about Schizophrenia, many times, we think in terms of hallucinations, delusions, paranoia, those are all characterized as the positive symptoms of Schizophrenia. For the last few decades, when I got into this business a few decades ago, one of the first things I did was do a collaboration between my company and a large pharmaceutical company with a drug that we hoped would help treat the negative symptoms of Schizophrenia. And I remember at that point in time, talking to KOLs and they said the most significant unmet need we have today is negative symptoms. And those are the symptoms that manifest in the social withdrawal aspects of the disorder that lead to low social functioning, long-term disability and very significant caregiver burden. Today, 29 years later, we've not moved a niche on negative symptoms of Schizophrenia. There's still no drug approved to treat those symptoms. Drugs that treat the positive symptoms sometimes haven't -- many times have an indirect benefit on negative symptoms, but it still leaves almost half of the patients -- of Schizophrenia patients with predominant negative symptoms that are untreated with no drug approved. Our approach here with Pimavanserin led us to run a pivotal study. We call our ADVANCE-1 study in negative symptoms of Schizophrenia. And what we achieved here is something that's been rarely seen in negative symptoms. We have a positive pivotal study. As you can see here, we had a little bit of dosing flexibility here because we wanted to explore a dose range. So what we see here is when we look at all 3 doses tested, we have a statistically significant positive result, p-value of 0.043. Importantly, though, at the tie dose, the 34-milligram dose, that's the same dose that were approved to treat Parkinson's disease psychosis patients, we saw a significantly stronger effect in that group, p-value of 0.0065. So again, something we rarely seeing, negative symptoms of Schizophrenia. We're very excited about these results. And on the basis of these results, we are now nearing the completion of enrollment in a second pivotal study, our ADVANCE II study. There are 2 key differences between ADVANCED I and ADVANCED II, both of which are designed to increase the probability of success. One is, I mentioned that -- we allowed for some dose-ranging work in ADVANCED I, but with much stronger results when we look just at the 34-milligram dose. So in ADVANCED II, we're only studying the 34-milligram dose. Again, that's the dose we're proven in PDP. There's clearly the most efficacious dose here. So the fact that we won't have other doses in patients on lower doses that have a dilutive effect, which should benefit the probabilities of success in the state. The second is it's well established. The FDA has even commented on this publicly, that it's -- over the last 4 decades, it's become increasingly difficult to show -- to separate from placebo in Schizophrenia studies conducted in the United States. It's very well known if you follow other companies developing antipsychotics. I'm sure you've heard about this. And that -- I don't have time to get into why that's the case, but it is the case. Is it primarily deal is result of the way we treat Schizophrenia in the United States versus the way it's treated in Europe and other parts of the world. And so in ADVANCE-1, we studied enough patients in the United States. We don't need to study more. So ADVANCE-2 is being conducted entirely outside of the United States. So that typically makes it easier to differentiate versus placebo. So again, we should complete enrollment around the middle of this year and with results a little over a year from now. We're going to move now to our earlier portfolio. Most importantly, I'll -- I'm going to start with ACP-204. So with Pimavanserin, we have a very successful drug with a robust antipsychotic effect in a very, very positive safety profile and tolerability profile. We're taking those learnings, and we've applied them to several other molecules, the most advanced of which is ACP-204. We have some others in the pipeline as well. I'm going to focus on ACP-204 for now. So again, we're leveraging the learnings we have, both Pimavanserin or NUPLAZID and ACP-204 worked primarily by blocking 5-HT2A. So that conveys certain benefits in this very favorable tolerability and safety profile. With Pimavanserin, we do have a little bit of baggage that -- and it primarily relates to a modest QT signal. If this were a drug to treat Schizophrenia patients, it would pretty much be a nonissue. Those drugs are prescribed by psychiatrists. They're very comfortable with polypharmacy. They -- a majority of those drugs have QT elongation signals. So they're very comfortable with that. They dose those drugs on top of other drugs that have a signal, and it's not a concern to them. When you get to elderly medically compromised patients, in Parkinson's disease or in this case, Alzheimer's disease psychosis, it is a very different situation, and they're dosed many more times by neurologists who aren't as comfortable with polypharmacy. And just given the medical condition of these patients, they're more focused on things like QT elongation. So one key design element of ACP-204 is to minimize or potentially eliminate the QT signal. And based upon the Phase I data we have to date, it appears that we've done that. So again, more to come on this, but all the day we have so far is lining up with the design elements that we put into the molecule. There are other elements of the molecule that may lead to increased efficacy. There's actually an indirect benefit to minimizing the QT signal here in addition to it just making it easier for the physician to prescribe and think about and think about co-administering with other drugs that may have a QT signal elongation. We just couldn't go any higher on the dose with NUPLAZID, 34 milligrams as high as we could go based on the QT signal that we saw. And so there may be more that we can get out of this mechanism if we, again, have minimized or potentially eliminate a QT signal. Pimavanserin or NUPLAZID also takes 12 days to get to steady state. We often see that kind of dynamic with serotonergic drugs. So it takes 2 to 3 weeks before patients begin to see a benefit of the drug. The dopaminergic drugs used off-label have a much faster onset of action, you typically begin to see benefit within a few days. ACP-204, we now know, based upon human work that we've done, we should get to steady state in about 5 days. So much closer to the onset of activity that we see with dopaminergic drugs. I mentioned we're in Phase I. I think in most cases, if this were a Phase I asset, we probably wouldn't spend as much time talking about it as we do. But because this drug is both chemically and biochemically closely enough related, I'll state it that way, to NUPLAZID, it just has a different risk profile typically small molecules, early development, very high attrition rates. But we're working with a mechanism that we know really well. We're working in a chemical space that we know really well. We know the moving nitrogen around this way or that way does this and does that. So we're working in a space that significantly derisked for a market opportunity that is dramatically large. So we're very excited about this program. We're eager to finish up Phase I, more to come on our Phase II plans, what we've done now. Last topic I'm going to cover is business development. And the reason I -- we have a slide on this, it's just a very important part of our business. Trofinetide is a good example of our success in business development. We acquired rights, North America rights that compound after the completed Phase 2, we're now on the cusp of a potential approval and launch of that drug. We've done a lot of business development. There's a lot more that we will be doing. And my point here is just to simply give you a little bit of additional texture around our plans and what you should expect to see from a business development perspective. We have a footprint both in psychiatry and neurology, broad indications, rare disease. I think NUPLAZID is a good example of this. It's a drug to treat psychiatric symptoms, but it's prescribed almost exclusively by neurologist. So we're in neurologist offices all the time. Of course, trofinetide is a rare disease. It's more neurology-based and so as we go forward, what you should expect to see is keeping a footprint in all 4 of these quadrants, but the mix will shift more toward rare and neurology. And that's really a function of where other companies that you might be hearing speak at this conference and their venture capital investors have been putting their resources. So we did a survey a few years ago and say, well, where are VCs investing in the CNS space. And what we see it's heavily -- been heavily weighted to neurology and rare. There's some really good reasons why that's the case. And so for a company that grows our business through transactions, that's where the opportunity is for us. The opportunities, I should say, are just richer in those quadrants than they are in the broader indication. Again, we'll continue to have a footprint in all 4 of the quadrants, but you'll see the mix shift as we go forward. Last thing I'll say about this is we're all very aware of the capital market environment. I've been waiting for this day for 6 or 7 or 8 years. It's a company that does a lot of business development, the most significant competitor we've had have been you. You've been investing in these companies and funding them, and it's been very difficult to get deals done. It's a different capital environment now, and that really benefits us. We don't need to raise additional capital, a lot of other companies do. And we're already beginning to see the impact of that. It's definitely making companies more amenable, more eager, more actionable than just frankly would have been a year ago. But just still all this down into our near-term milestones, trofinetide PDUFA date, March 12, Pimavanserin negative symptoms of Schizophrenia will complete enrollment in the middle of this year. Again, top line results a little over a year from now. And in Alzheimer's disease psychosis, or ECP-204 molecule will complete Phase I in the first half and very eager to get this drug into Alzheimer's disease patients soon after that. All right. I think we'll go to Q&A now.

Thanks, Steve, for the presentation here. Looking at my clock, we only have about, I don't know, 5 or 6 minutes for Q&A. And we have a number of portal questions that have come in from you guys as we've been chatting here. So I'm just going to jump right into them. So the first question that we have here is how is the review of trofinetide going? And have you completed the mid-cycle review yet?

So the answer is exactly according to plan. From everything that we can see, we never know exactly what's going on by the doors of FDA. We have had our [indiscernible] review meeting. Our policy is not to talk about the specific interactions we have with FDA when we've got a drug under review. But what I can tell you is from everything we can see in terms of their level of interaction, the feedback we got after the midsole review meeting, et cetera. They appear to be exactly on track with where they should be. And we can assure you they've been very engaged. I'll just compare and contrast for a second. We had an application under an SNDA, so a supplemental drug application that many of you are familiar with. And under an sNDA, the FDA does not have to hit certain milestones. They're not required to communicate as they are as much as they're an NDA. And we just frankly didn't get a lot of communication back on the SNDA. This is a very different situation. They've been very engaged with us. And again, we're eager to get to March 12.

Okay. And second part of the question is, is there any indication that there might be an ad com may know that there wasn't back in September. And given how many PDUFA extensions we have seen since the pandemic, do you believe that the review is tracking as expected? It sounds like you do.

So yes, on the second part, everything we can see, and again, we're very engaged with them, they appear to be, and they certainly tell us explicitly we're on track. I think in terms of AdCom, when we -- when they accepted our application for filing. They said, we do not plan to have an AdCom. After the mid-cycle review, they reiterated that. It's always possible. I mean, sometimes, I mean there are human too, sometimes things come up at the end of a review and they think we just need more time to explore this or we need -- now we think we need an AdCom. So it can happen, theoretically can happen. But at this stage of the review with March 12, PDUFA day, I think it is exceedingly unlikely that we'll have an ADCOM and the FDA has continued to tell us, we do not find an AdCom.

Okay. Great. And another question that we got through e-mail was just around pricing for trofinetide. And are there any kind of comps we should be thinking about as we kind of think about a potential price here?