Good morning, everyone. Welcome to our second day of our Piper Sandler Healthcare Conference. My name is Yaz Rahimi. I'm a senior biotech analyst here at Piper Sandler. So thrilled to have LB Pharmaceuticals with us. Heather, wonderful to have you. I had the pleasure of meeting Heather last year during our conference when the company was private. She had just joined, and I cannot believe what it has been, an incredible year, after joining, reporting the phase II-B data, getting the company ready for an IPO, having a very successful IPO in a very, very tough market, and with sufficient capital to kick off the phase III studies. Really incredible. I cannot believe you did all this in 12 months. Yeah, it went by very fast. It went very fast, but she did it all with an incredible team that's here with us. So really thrilled to have you here. Thank you for having us. Wonderful. So lots to cover. I guess a good place to start off is a big objective in 2026 is obviously getting the phase III study in schizophrenia, and the target is Q1. So just give us a quick update: where are you in the process? And let's start there. Coming out of the IPO, we actually now had the capital, so we could really work on getting these trials initiated in earnest. So we've been heads down in execution mode, working to get all of the sites up and running, getting the drug supply ready and available, and really putting ourselves in a position to get this trial started in the first quarter. So it's really just been execution mode coming out of the IPO. Obviously, you can't enter into contracts until you have capital, so that was one of the biggest gating items. But now it's all systems go. Perfect. What is the disclosure going to be? Sort of the cadence as? Yeah. We plan to announce the first site open for both of the indications, for both schizophrenia and bipolar depression. Team, recently you also noted too at earnings that you plan to upsize the study from 400 to 460. Maybe help us understand, one, what was the rationale behind upsizing it? And two, what does that additional size mean in terms of the powering assumptions of the study? We did increase the sample size, as we noted in our earnings release. We did this to increase the statistical powering of the trial. So we took the trial from 80% power to 85% power. We think this was a prudent use of our capital. And it didn't change any of the timelines or the assumptions around the clinical trial. It's the same number of sites. It's the same geographic region. It's really just about increasing the N. And the timing of the trial continues to be on track. We still expect to announce top-line data in the first half of 2027. So it didn't change anything. We just think that it's prudent to have the higher statistical power. That's very helpful. And, Team, one other thing, just in the weeds that sometimes you probably will get in your meetings all day, but let's clear that is: whether the assumptions affected at all the upsizing, if it affected any assumptions related to discontinuation rates, placebo responses? We powered the trial to have a PANSS delta versus placebo of six. So that continues to be the case. So it's powered at 85% for a PANSS delta of six. We aren't going into the details around the standard deviation or the discontinuation rates that were assumed. What we say is that it is consistent with what has been observed in other schizophrenia phase III trials and is more conservative than what we observed in our phase II trial. Okay. And then the NOVA S tudy, between the phase III and the phase II study, there are a lot of common elements. Maybe it's overlap of the sites and PI is the same. The highest dose, the field selection is the same. Maybe the only change, and correct me if there's any other changes or differences, is the change of the moving from 28-day primary endpoint to 45. So why did you go to 45? And what does that do in terms of treatment effect, and what does it do when we go to, I guess, two more weeks in terms of treatment arm as well? There are a few differences between our phase II trial and our phase III trial. The scale and scope of the two trials, as you mentioned, are very, very similar. In terms of the differences, you're right that the phase II trial was four weeks in duration. We're planning the phase III trial to be six weeks in duration. We're doing this for two reasons. One, we looked at the curves of efficacy from the phase II trial, and they haven't flattened. So we think that there's an opportunity to see further efficacy with a six-week trial. We also know when looking at other schizophrenia trials that extending the trial from four to five to six weeks does result in further separation from placebo. One of the other differences is the fact that the phase II trial was a four-arm trial. Our phase III trial is a three-arm trial. We think this will help with the placebo rate. We know that with every single arm that you add to a schizophrenia trial, you do run the risk of increasing that placebo rate because patients have a higher probability of being on an active therapeutic. And so we think that having less arms is going to be better. Another change that we're making is we had evaluated cognition as an exploratory endpoint in the phase II trial. And in the phase III trial, because of the robustness of the data that we saw in the phase II trial, we've elevated it to a secondary endpoint. The reasons that we're making these changes is we think we'll have further efficacy. And we also think we'll have a better probability of success because we'll have a better opportunity to manage that placebo rate. Okay. Wonderful. And then, Turner, one of the parts of the study also includes to do a blinded standard deviation assessment, which also gives you another opportunity to do a sample size calculation. Maybe help us understand, can you provide a little bit more detail on that, on when that could occur and what the rationale for incorporating that and whether that's something you would also disclose to us once it occurs? We do have an opportunity to assess the standard deviation in a blinded fashion. We aren't providing any specifics around the nature of that or the timing of that. And if or when we decide to do that, that is something that we'll get into later as we progress into the trial. Okay. And what have you publicly said in terms of, given that there's a significant site overlap between the phase II and phase III in terms of enrollment timelines and when the phase II could read out? There are quite a bit of similarities between the phase II and the phase III. As I mentioned, the scale and scope is very similar. The phase II trial had 25 sites. We're targeting 25 sites for the phase III trial. The geographic region is the same. It's just in the U.S., and it's around the U.S. regionally. In terms of the timing of the trial, what we've announced is we expect top-line data in the second half of 2027. We don't anticipate providing specific details on enrollment. Okay. That's very helpful. Maybe you noted that the study is powered 80% power to show a 6-point PANSS score. The phase III is pretty large study. Help us understand Post-hoc data. What is the regulatory requirement for approval in schizophrenia and whether this single pivotal study would be sufficient? Yeah. Coming out of the phase II trial, we had an end-of-phase II meeting with FDA. And we asked FDA whether they considered that trial to be registrational in quality. We designed that trial to be registrational in quality in terms of the sample size and the sensitivity analyses and the way that we conservatively imputed missing data. And FDA concurred in writing that that trial did have the characteristics of an adequate and well-controlled trial. Coming out of that, we think that opens up the opportunity for a streamlined path to approval with just one successful phase III trial. As a result, we are intending to have everything that we would need in order to seek approval coming out of that phase III trial. So if that phase III trial is successful, we will have accrued the safety population that we need. We're intending to start an open-label safety study so we could accrue the 1,500 patient exposures that we'll need. We're also executing on all of the NDA enabling studies in parallel so that upon successful completion of a phase III trial, we're ready to submit for approval and to go into a pre-NDA meeting with FDA. Thank you. Maybe it would be great for investors who are new to the LB story and who are trying to understand LB- 102. You could talk about, maybe before you talk about the differentiation, is to help them understand Amisulpride, its availability in Europe, how it's used, its product profile, and then contrast it to the differentiation versus LB- 102. Amisulpride is a derivative of Amisulpride. Amisulpride is an antipsychotic that has been approved around the world. It was never approved in the United States. It's considered one of the more safe and tolerable antipsychotics with a significant amount of efficacy. It has a treatment effect second only to Clozapine in terms of efficacy. It's also very widely used. In 2024, there were 2 million prescriptions issued for Amisulpride, and that's without any sort of commercial or promotional marketing at all. Of those prescriptions, 20% were in mood disorders. So it continues to be widely used, not just in schizophrenia, but also mood disorders. It has approvals in schizophrenia and predominantly negative symptoms of schizophrenia, as well as dysthymia, which is a chronic form of depression. It does have a challenge. Amisulpride has very poor blood-brain barrier permeability, and this results in the need for high doses. For schizophrenia, it's dosed between 400 and 800 mg a day. This makes it so it's not amenable to a long-acting injectable. It also requires twice-daily dosing. The founders of LB Pharma wanted to create a molecule that could result in a new chemical entity, as well as composition of matter, intellectual property, and maybe solve that limitation on permeability. And they did this through methylating Amisulpride. So we added a methyl group to the structure of Amisulpride, and that methylation improved the lipophilicity of the molecule, which improved the ability to penetrate into the brain. And this resulted in a more potent molecule. LB-102, we know at 50 mg is about the same as 400 mg of Amisulpride. And this is based on the dopamine receptor occupancy data. Both of those are 70% dopamine receptor occupancy data. We also have once-daily dosing. The molecule LB-102 has a longer residence time in the CNS, which enabled once-daily dosing, and this is important because we know in this patient population, compliance is improved when you have once-daily dosing. The other aspect that we were able to show is that we have the potential for a better tolerability profile. We have less systemic exposure as a result of the improved potency, and we think that this can improve the tolerability profile as well. Thank you. That's very helpful. And maybe one of the questions that we often got during the roadshow is, if you took the phase II data from the NOVA S tudy and you compare it to branded schizophrenia therapies, how does that compare, right, with the assumption you reduced that in your phase III, both across its effectiveness as well as safety? It would be great if you could just kind of compare and contrast that, and then also maybe overlay how you think LB-102 positioned in the schizophrenia market. We think LB-102 has the opportunity to be a branded therapeutic of choice among the antipsychotics. The treatment paradigm for antipsychotics is patients have to take one or two generics before they're able to take a branded. So it really comes down to whether or not you'll be the branded antipsychotic of choice. The reason why we think we have the opportunity to be the branded antipsychotic of choice is we do have competitive efficacy. We believe that our molecule would be used to treat patients with acute schizophrenia. We also think we have the potential for a best-in-class safety profile among the D2 Antagonist and the partial agonist. This is predominantly as a result of the low rate of EPS or extrapyramidal symptoms that we observed in our phase II trial. At the 50 mg dose, we saw just 1% of EPS. There was only one case of akathisia at the 50 mg dose. At the 100-milligram dose, we saw a rate of 5.6%, and placebo had a rate of 3.7%, so this is a very low rate of EPS. When you look at partial agonists like Vraylar, for example, which is one of the widely used antipsychotics, it has a rate of EPS of anywhere from 24%-32%, so it's quite high in terms of this adverse effect. If you look at other D2 Antagonists, including Amisulpride, they tend to have rates of EPS in the teens, so this was a very low rate of EPS that we think is real. We saw 251 patients that were treated with LB-102, and we saw this very low rate of EPS. We also think we have an opportunity for differentiation in two domains that have significant unmet need in schizophrenia. The first is cognition, and the second is negative symptoms. I mentioned that we measured cognition as an exploratory endpoint in our phase II trial, and in that, we observed a treatment effect at the high dose of 100 mg of 0.66. This is a very high treatment effect in cognition. This is one that we think is quite interesting and something that we would really like to explore further in other clinical trials as well as mechanistically. We know that the mechanism of LB-102 has the potential for a pro-cognitive effect. LB-102 is a strong and selective Antagonist of D2, D3, and 5-HT7, and D3 and 5-HT7 are both pro-cognitive. The other domain is negative symptoms. At the 50 mg dose in our phase II trial, we saw statistically significant benefit to placebo in treating patients with negative symptoms, and this is based on the PANSS negative symptom subscale. This is consistent with what is observed with amisulpride. When amisulpride is used to treat depressive-related symptoms, it's used at lower doses. So we do think there's an opportunity here to have a differentiating effect on both negative symptoms and cognition. Very helpful. Maybe just a couple of questions that also always come up during the IPO, which you will also frequently get, which just reminds people is, why was Amisulpride never registered here in the U.S.? And maybe we'll start there. So Amisulpride was approved a very long time ago. It was approved in the late 1980s. And it was originally developed by a very small biotech in France. That biotech was eventually acquired by Sanofi. When Sanofi acquired that biotech, it set out to bring Amisulpride to the United States. And when they engaged with FDA, FDA insisted on a full development program. And conducting a full development program in the United States was not compatible with the IP life that remained in the United States. So the decision was made not to bring it to the United States. So physicians have never had the opportunity to prescribe Amisulpride in the United States. And interestingly, it's something that we've heard from some physicians about. They lament the fact that they haven't had the chance to actually prescribe it here in the United States. Thank you, and then another question that we often got is, when we look across, have you had the opportunity to look across other schizophrenia studies and looked at what happens when you go from a phase II study to a phase III? Of course, Heather, you provide an incredibly thoughtful summary on how many elements of the phase III is aligned with the phase II that reduces very minimal changes. But historically speaking, could you maybe talk about that or what the treatment effect looks like? It is the case that when you go from phase II to phase III, you do tend to see a lower treatment effect. You also tend to see a little bit higher of a placebo rate. The two things that give us confidence in both of those regards is the fact that we had a very robust treatment effect in phase II. If you look at it conservatively, the treatment effect we observed in phase II is on par with or even better than Caplyta, depending on the dose that you look at. With respect to the placebo rate, we implemented a number of measures in our phase II trial to help manage that placebo rate. One of the most important attributes of that is really identifying and excluding professional patients. This is, unfortunately, an aspect of these trials that can really negatively impact your placebo rate. In our phase II trial, we utilized one vendor to help us identify these professional patients. In our phase II trial, we intend to use two vendors to help us identify these professional patients. We also will do all of the other measures that we implemented in phase II to help manage this placebo rate, the most important of which is that frequent, consistent engagement and management of your clinical trial sites. This is why we kept the number of sites to a manageable number. This is why we kept the geography to the United States, because we think this is a very important aspect of conducting this trial. Thank you. That's very helpful. Maybe we'd love to spend the next five minutes on LB-102 and its development in bipolar depression. Maybe help us understand, it is approved, right? Amisulpride is approved in bipolar depression. It actually has no approvals in any of the bipolar disorders. So this is a global opportunity for LB-102 and one that we are very excited about. Amisulpride has history and clinical data in depression. It's been used in depression. There are clinical trials that have shown that Amisulpride is statistically significantly better than placebo when it comes to treating depression. And it's also been shown head-to-head with Paxil and Zoloft to be as good or better than two of the leading antidepressants that are used. So there is clinical evidence. And where are you sort of envisioning? Where are you in development? You have, during the IPO, some of the proceeds will go towards funding the phase II development. Maybe help us understand study design, how you selected doses, and that study and what the rationale behind it was. We plan to start the phase II clinical trial for bipolar depression in the first quarter of next year. This is a trial that will be a two-arm trial. We'll be evaluating two doses in this trial. So we'll give ourselves maximal opportunity to demonstrate a response while minimizing that placebo rate. We know that in depression trials, every time you add an arm, you can increase the risk of that placebo rate going up. So maintaining a two-arm trial, we think, is very important. Patients will start at 25 mg. At the end of week three, they will escalate to 50 mg if they have not improved based on the CGI-BP scale. And then they'll stay at the 50 mg dose for the remainder of the trial, which is another three weeks. So it's a six-week duration trial. We're targeting about 320 patients at 30 sites in the U.S. The doses that we chose for this trial are 25 and 50. There's basically two dosing paradigms in bipolar depression. You've got one is where you have drugs like Vraylar and Latuda, who actually have very high rates of EPS. For bipolar depression, they had to take their schizophrenia dose and cut it in half because they really needed to lower the rates of EPS. Even with half the dose, they still actually have pretty high rates of EPS. Vraylar and bipolar depression have rates between 10% and 16%. The other dosing paradigm is Caplyta. Caplyta has a very low rate of EPS, so it was able to maintain its schizophrenia dose in bipolar depression. So we're able to do both. Because we have such a low rate of EPS that we observed in our phase II trial, we're able to evaluate both the schizophrenia dose as well as half of the schizophrenia dose, and that's why we chose 25 and 50. Okay. That's very, very helpful. And then maybe in two minutes, to talk about the long-acting that you're also developing, where are you in development, how do you envision sort of the disclosures in 2026? Because we were successful with the 50 mg dose in the phase II schizophrenia trial, we believe that a long-acting injectable is feasible for LB-102. I mentioned before that Amisulpride is not amenable to a long-acting injectable because the doses are just too high. This then provides a global opportunity for the long-acting injectable. We plan to interrogate and investigate the formulation for a long-acting injectable over the next year. The goal here is to have a subcutaneous once-monthly injectable that wouldn't require any sort of loading dose. That's the objective. That's what we'll be working on over the course of the next year. When we have meaningful success, we'll be sure to announce that. Perfect. And then the last question is, with the proceeds of the IPO, what is the current cash and the cash runway to get you through all three developments? Yeah. In the IPO, we were able to raise a net of around $300 million. So we were able to upsize the deal greater than we had anticipated, which is obviously great for our programs. As a result of that, we were able to fund the schizophrenia trial as well as the bipolar depression trial and all of the work that we need to do in order to put ourselves in a position to seek approval. And that gives us capital into the second quarter of 2028. So we're well capitalized beyond the two data readouts. Maybe if I can give some commentary too, with the first IPO where they came up with an evaluation that people were scratching their heads because they saw competitors, right, getting acquired at $14 billion. Heather, if you want to talk through that quick, a lot of credit goes to you guys, which I've never seen in my career on the numbers picked as you guys were going out. Yeah. It was really important to me and to the company to really capitalize the further development of LB-102. We think LB-102 can bring tremendous benefit to patients. We knew going into this IPO process that valuation was going to be a critical component of success. We decided early on to do a truly market-driven IPO process where we allowed investors to talk about and dictate the valuation. That is really what I think allowed us to get this IPO done, was to have a valuation that was really one that was driven by investors versus inside investors. We think that was the difference maker in our ability to get this done. A tremendous amount of credit goes out. It was a very, as you guys all know, at the beginning of the year, it was a very tough market for biotech. And LB Pharma was the first IPO to go out very successfully and open the door. So I really do think that they need a big applause for what they did because they opened the door. Well, thank you. Yeah. And we're excited that the stock price has actually maintained. Yeah. That's an added bonus. Also never happens these days. So yes, a second applause. Thank you so much. Thank you so much.