Okay, we're ready to get started. Welcome, everyone, and thank you for joining us for today's Virtual Investor Closing Bell. My name is Jenene Thomas. I am CEO of JTC IR, and I will be the moderator for this event. So, the Closing Bell series starts at market close and allows for companies to share an overview of their story and connect with investors. For this session, I am very pleased to be joined by J.D. Finley, Chief Executive Officer, and Dr. Mitchell Jones, Chief Medical Officer of Palisade Bio. Welcome, gentlemen. Thanks, Jenene. So happy to have you. So, for today's event, we will start with a corporate overview from J.D. and Mitch, followed by a Q&A session. Before we get started, I just want to remind our audience that Palisade Bio is publicly listed on NASDAQ and trades under the ticker PALI. Without further ado, I am going to turn it over to you, J.D., to kick things off. Great. Thanks, Janine. Next slide, Mitch. Before we get started, let me remind everybody that during today's presentation, we will be making some forward-looking statements, and I encourage everyone to view the company's website at palisadebio.com or the SEC's website for our latest filings and information. That next slide, I'll give a quick overview about the company and then turn it over to Mitch, who will get into the details of the science and the drug. Just to start with, our focus as a company is on advancing early-stage drugs, addressing immunology and inflammatory diseases, and especially those that may have a fibrotic component. We're very excited about our lead program, which is a PDE4 inhibitor targeting all sorts of colitis and Crohn's disease, and can't wait for Mitch to give you a lot more details on that. It's a small molecule that was initially developed in the Merck labs in Montréal, in the Montréal facility. As many of you are aware, inflammatory bowel disease is a multi-billion-dollar market, with many early-stage drugs being sold to Big Pharma for several hundred million dollars on the low end and up to several billion dollars on the high end. Very excited about that. Next slide. If you look at our development pipeline, we're currently developing two drugs with this molecule. Our lead drug, PALI-2108, that's focused primarily on all sorts of colitis, and we're finishing up our preclinical studies, and we're about to start our human phase I studies in just a few weeks. We believe our lead drug has several key advantages over the current therapies in this space, as Mitch will cover here in a few minutes. Next slide. As I mentioned, Big Pharma has been very active in the space. Here's a list of some of the key acquisitions that have been done recently. You can see they're spending anywhere from $hundreds of millions up to $billions for drugs that show promise in addressing this disease. It's important to note that some of these deals that were completed for fairly sizable dollars were still in the preclinical phase. With that brief overview, let me turn it over to Mitch, who can provide the details around the science. Thanks, J.D. Yeah, so the drug is PALI-2108. It is a prodrug, as J.D. pointed out. The PDE4 inhibitor was developed at Merck. However, the prodrug, which is a sugar bound to the PDE4 inhibitor with a bond that is released by the bacteria and enzymatic milieu of the colon, was developed by the founders of a company: Giiant Pharma, who we licensed all the technologies and PALI-2108 from wholly. So, speaking about ulcerative colitis, there's still significant unmet medical need in ulcerative colitis. There's a need to improve remission rates. Clinical remission rates are still an average of 16%. Most of the approved drugs are below 20%, certainly in terms of three-month clinical remission. A minority of patients gain clinical remission with any one drug, but 30%-40% fail first-line biologic therapy overall. There's also a need for disease-modifying agents to prevent the sequelae of disease, including removal of the colon or colon cancer. There's a need for optimized or tailored treatments. So, identifying which drug and which target for which patient is important for which patient. And there's also a need for oral treatments. There's two oral treatments in the market, including a JAK inhibitor, or two oral targets in the market: JAK inhibitors and S1P modulators. And JAK inhibitors come with a black box warning, and there's risk of liver dysfunction and infection with S1P. So, there's a need for oral treatment, certainly. Patients and clinicians are asking for those. In terms of our differentiators, PDE4 is a novel target and pathway in the space. There's compelling phase II data. We're oral, locally active, and this improves the therapeutic window for PDE4 inhibitors. We have really nice data demonstrating the proof of concept and efficacy and gold standard models. We've done a number of studies, including ex vivo studies showing release of the drug as well as the anti-inflammatory capacity. Looking now at current therapies, on the left, you've got TNF blockers, integrin blockers, and Entyvio, the 12/23, Stelara. You've got the JAK inhibitors, the S1P modulators, and again, another IL-23 there on the far right. Many of these are IV or subcu. A number of them are oral. Many of them come with black box warnings. So, again, there's clinicians, patients really looking for oral therapies, looking for more efficacy, and certainly not black box warnings or serious risks. So, the market's growing, and the growth is coming from oral treatments. So, you can see S1P modulators and JAK-STAT inhibitors are where the market growth is coming from. This is the addressable population. We plan to treat moderate to severe UC patients, and we plan to treat patients with elevated PDE4 activity. We think that's the vast majority of the moderate to severe population. In terms of the opportunity, there's significant unmet need. We've talked about that. Disease burden's high, limited efficacy. Patients are failing to respond. We believe there's an opportunity for precision medicine in PDE4, and we've got data supporting the fact that we can likely select patients that will respond to PDE4 inhibitors. This all results in a large market opportunity, especially with premium pricing. In terms of de-risking elements, Otezla, apremilast is a PDE4 inhibitor that is delivered orally and is distributed systemically. There are dose-limiting side effects to these drugs: nausea, headache, vomiting. In comparison, our drug 2108, sorry, there's a typo there, but it's locally delivered. There's a lack of systemic exposure and improved therapeutic window and 20 times more potent TNF inhibition. Looking now at, again, we were talking about de-risking, looking at phase II data from systemically delivered PDE4 inhibitors. On the left, you've got mild to moderate ulcerative colitis patients demonstrating a dose response. And on the right, you've got significant clinical remission in the low dose and then loss of response in the higher dose group for apremilast. The significant response in the 30-mg dose was at 31.6% clinical remission over a placebo of 12%. And at the high dose group, some patients in the 52-week cohort discontinued therapy due to nausea. So, we believe that some of those patients are discontinuing therapy and not compliant, but also the 30-mg and the 40-mg BID groups are very close in dose. Our mechanism of action here, we're a tablet. We're coated and delivered to the distal parts of the small intestine. The coated tablet dissolves quickly, moves to the colon, where it releases the PDE4 inhibitor when acted on by the enzymes in the colon. The PDE4 inhibitor acts intracellularly on PDE4 to inhibit its action on cyclic AMP. Cyclic AMP levels rise, inhibiting TNF alpha, increasing the anti-inflammatory cytokines, and preventing cells from entering the inflamed tissues of the colon. This is a slide demonstrating the improved therapeutic window. You can see the colon, the blue bar graph there, showing that basically the active drug is released in the colon. This is a number of graphs showing the results of our DSS mouse study demonstrating an improvement in body weight, an improvement in disease activity over disease. The ulcerative colitis group in this study shows body weight. As you treat with the drug, you see body weight improvements. As you can see here, the green bar is disease. It's ulcerative colitis. And then you have treatment with drug at low, medium, and then high doses, where with respect to disease activity, those doses are improved over standard of care. And on the far right, you've got the purple graph here, which is twice the dose of apremilast used in phase II clinical studies, and that was effective. And so that dose in mouse, when you look at that dose in human, you couldn't use that dose due to the systemic side effects: nausea, vomiting, and discontinuation of therapy. Colon length is one of the primary endpoints, clinical endpoints of these studies. And you can see that as you deliver more 2108, you have an improvement in colon length up to similar to standard of care. But you can see here on the left-hand side, you have PDE4 expressions elevated with DSS colitis. And then as you treat with the drug, PDE4 goes down. You have cyclic AMP levels increasing over time and TNF alpha levels that are reduced to normal. Then this slide, looking at our precision medicine approach, we have collected 1,700 patient samples and data. We've looked at expression-level data in colon samples and also used clinical outcomes to evaluate the PDE4 E effectors, that is, the proteins that are effective when treating with PDE4s. And we've compared that to all of the biomarkers that change with disease in ulcerative colitis and are associated with worsening disease and disease severity. And we found that subset 40 PDE4 effector genes are also responsible for ulcerative colitis disease activity. And so we plan on using those and a computer learning technique to be able to predict response. And so you'll see that on the next slide. We have our clinical plan. On the left-hand side, you've got a phase I study with single ascending dose, multiple ascending dose groups, as well as an ulcerative colitis patient cohort. That cohort, we plan to select from about 20 patients with ulcerative colitis. We'll take a sample, look at the transcriptomics data. We'll look at those 40 biomarkers and select a group, a smaller group, to treat for seven days like the multiple ascending dose cohort, and then look at the response from a pharmacodynamic perspective. Then we'll take those data into our phase Ib study, where we'll treat with a couple of doses, and we'll look at those PDE4 effe ctor biomarkers and use computer learning to identify a signature that we can use to select for patients in our phase II study. Within the phase II study, we'll select patients that are moderate to severe and are high PDE4 expressors. So, looking at the development plan, we're currently in IND CTA enabling studies. We have interactions with regulatory bodies coming up in actually next month or within 30, 40 days. We plan to start our phase I study, and before the end of the year, we'll have a patient into the SAD cohort with top-line data in the first half of 2025. We plan on starting the phase Ib, 2a study in that timeframe as well, with a readout of the 1b roughly a year later and the 2a a year after that. This is a slide speaking to some of the upside potential for 2108 and the related program 1908. We believe that it's a PDE4 inhibitor, antifibrotic, anti-inflammatory. It could be used in fibro stenotic Crohn's disease as well as PDE4s being evaluated in other diseases such as IPF. The slide speaks to the IP portfolio. We have composition of matter coverage up to 2042. We have, of course, there'll be regulatory coverage for eight years, and we plan on filing additional patents. Those could be formulation, methods of use, and platform. J.D.? So, here's a look at the leadership team that's developing this asset. Everyone here has deep development experience. Just to point out, the four people on the upper half of the slide are full-time employees of Palisade Bio, and those on the lower half are key third-party consultants. We encourage you to visit our website to learn more about the leadership team beyond just me and Mitch. Next slide. Okay. Then here are the two industry leaders who serve as our clinical advisory board. We're very excited to be working with Dr. Sands and Rieder. Both of these guys are renowned experts in the IBD world. Those of you who are familiar with this space have probably heard of both of them. Dr. Sands is widely recognized for his innovative treatment of IBD and for his clinical investigations in new therapeutics specifically. Then Dr. Rieder is the leading principal investigator on the International Stenosis Therapy and Research Consortium, more commonly called the STAR Consortium. He has a very heavy focus on fibro stenotic Crohn’s disease. Next slide. Then taking a look at the financial snapshot, we reported $11.3 million of cash as of March 31, our last quarterly filing. And that does not include the proceeds from a $4 million private placement that we closed in early May. Right now, our cash takes us through late Q1 of 2025. As you can see here, we're trading at less than half our current cash, and we traditionally have had strong volume in our stock with current average volume of over $1 million or 1 million shares traded daily. Next slide. So, kind of as a summary here, I think there are several key points to focus on. First, as we said at the beginning, PALI-2108 is addressing a huge unmet need in the ulcerative colitis space where we're seeing big pharma make many high-value acquisitions. And that's even with drugs that are in the earlier stage of development like ours. Second, PALI-2108 itself is very safe and effective. And I think it's differentiated in three ways just to kind of summarize some of the things that Mitch was saying. First, we're the only company currently developing a PDE4 inhibitor for ulcerative colitis. And as some of the science that Mitch reviewed shows, PDE4 inhibitors have been demonstrated to effectively treat ulcerative colitis. Second, and most importantly, by using an oral prodrug, it allows for local activation, which then significantly reduces the adverse effects seen in some of those other PDE4 inhibitors that have been used in clinical studies. And then third, by using a precision medicine approach, we believe we can increase remission rates by preselecting the patients that are most likely to benefit from our drug as opposed to others. And then the final point to make is that we believe, like many microcap biotech companies today, that we're significantly undervalued in the market compared to what we think our intrinsic value is, especially in our case where we're trading for less than half our current cash. And this is one of the reasons, I'll just tell you, this is one of the reasons that I have been and will continue to be purchasing our shares in the open market. And so with that, let me turn it back over to you, Janine. Great. Excellent presentation, gentlemen. Very exciting times for Palisade Bio. We are going to open it up to Q&A. So if you have a question, you click the Q&A button at the bottom of your screen, type in your question, and we will get to as many as time allows. While our audience is thinking of questions, J.D., Mitch, I see that you're building a rich pipeline in a space that has seen many high-value acquisitions from big pharma, right? So that's one of your taglines or one of the comments I hear you say pretty often. What is your overall development and commercialization strategy? Are you going to develop to a certain point and look for partnership? How do you view that? Yeah, I think that's right. And Mitch, feel free to weigh in on this as well. But I think our real expertise is taking these drugs in early stage and advancing them probably through the 2a, possibly 2b clinical studies, but at that point, handing them off to big pharma who is much better equipped to take it further toward commercialization. Mitch, what would you add to that? Yeah, I think that's right. I think we have that opportunity in ulcerative colitis, but also fibro stenotic Crohn’s. So again, proof of concept is sort of the biggest value driver. Great. And then just one more question. You showed on your slide the SAB and Dr. Sands and Rieder. Have they been associated with any drugs that have come to market? Mitch, you want to take that one? Sure. I don't know the complete list. I would say that for Dr. Sands, I would venture to say almost all of them, all of the recent ones. So he's definitely the primary author on a number of New England Journal publications for phase IIIs for recent approvals. But in terms of the list, I'm unsure. In terms of what Florian spends a lot of his time on, it's really the fibro stenotic Crohn's space. So I know that almost any drug that's being in early development in that space, he has his hands on. Great. All right. Great to see them working with you guys. All right. So we do have a bunch of questions that have come in. Our first question is, what% of UC patients have elevated PDE4 activity, and is there a commercial test for this available? That's a good one. Mitch? Yeah. I mean, so our bioinformatics analysis is based on looking at, again, around 1,700 patient data. So depending on how you define PDE4 activity, whether it's PDE4B levels or whether it's the enzymes that affect cyclic AMP or whether or not it's up to 40 biomarkers that we presented, it's somewhere between 60%-80% of patients, probably closer to the higher end of patients, have some form of elevated PDE4 activity, how we're defining it now. And so the second part of that question sort of goes to how are we going to measure that? In early research, we're going to look at RNA-seq data. And so eventually, something like a companion diagnostic regulated by FDA would be used to select patients. And so that could be looking specifically at proteins within ELISA, or it could be something more complex like an RNA-seq assay. Great. Our next question, what data are you looking for identifying patients that are likely to benefit from? How many patients do you need to build this database, and when will this be ready to go live? Yeah, Mitch, you want to take that one too? Kind of a follow-up last question. I mean, I can speak to sort of what we have done. So we've looked at thousands of patients' data and selected, curated around a database that's around 1,700 at this point. We are in discussions with, we've been the recipient through Giiant of an IBD innovation grant from Crohn’s & Colitis, and we work closely with their IBD Plexus folks. So we're in discussions with them. And so we can probably curate another database that can support the likely response. Now, when it comes to actual responders, that will be demonstrated in our phase Ib and 2a studies. Okay. Our next question, why haven't they used apremilast in UC? Do you think they eventually will? Apremilast has been used in ulcerative colitis in terms of clinical evaluation in a phase II study. They started with a 30-mg dose, which is the approved dose, which is sort of titrated. They titrate up to that dose in psoriasis or psoriatic arthritis as well. And so they evaluated the 30-mg dose and the 40-mg dose. And I think the results are somewhat mixed in that the lower dose was more efficacious than the higher dose. And so when we talk to experts, there might be a number of reasons for that. Some of them have to do with randomization and groups. Some of them, some KOLs believe that the 30-mg and the 40-mg dose are just too close together to sort of differentiate. I think in any case, we feel like the phase II data de-risks the approach. Then the other thing to recall is the preclinical data that we showed demonstrates that I think if you could go up as high as 60-mg BID with apremilast, you would see additional efficacy in colitis. At least that's what the preclinical data shows. So we pushed the dose to twice the equivalent dose of that 30-mg BID dose that was effective in phase II. And we saw a fair bit of additional efficacy in the mouse colitis model. And then we also demonstrated that we were able to achieve that with our prodrug locally. So we hope that that sort of demonstrates the concept and the potential for improved efficacy. Yeah, but let me make sure that we don't lose the key point here, which is apremilast could never be elevated to high enough doses to be commercially viable without triggering adverse events with patients. And I think that's the whole point of why we believe the prodrug approach that we're using is going to allow us to provide more efficacy with a PDE4 inhibitor than they could ever achieve with apremilast. Great. Okay. Our next question, what other diseases to target in IBD or otherwise do you think your prodrug technology might have high value? Yeah, we mentioned fibro stenotic Crohn's disease. I think there are diseases, other fibro-inflammatory diseases like IPF out there where locally administered PDE4 might be interesting. Okay. Our next question, what is the total addressable market and how do you see your drug fitting in? I think we address that basically moderate to severe and the fraction of those that are high PDE4 expressors or with high PDE4 activity. So we're expecting the sort of majority of the moderate to severe patients. Yeah. So it's an over $7 billion market today, which is projected to go to $10 billion in the next four years, four to five years. And so when you figure that we'll be addressing, we hope 70%-80% of that market, that gives you a sense of the potential of this therapy. Yeah. And these are patients feeling. Standard of care. Okay. And we do have a couple more questions in the queue. But to our audience, if you do have a question that you'd like to ask, click the Q&A button at the bottom of your screen and type in your question. Our next question coming in is, how do you ensure gastrointestinal restricted properties in humans? For example, have you validated gastrointestinal restricted properties using an artificial GI system? So we have evaluated this drug in dogs, in mice, DSS mice, so a disease model, colitis mice, as well as oxazolone mice. We have evaluated in monkeys as well, which is really close to human. And basically, similar properties among species. We've developed PBPK modeling for a mouse, for a dog, and a humanized model. And so there's a fraction of the drug which is absorbed well because it's a PDE4 inhibitor. It's an intracellular acting drug. It is absorbed, and it will circulate systemically, but it won't have the bioavailability of an orally delivered, high bioavailability PDE4 inhibitor that distributes at high 90s biodistribution and is absorbed in the small intestine. This is like a drug where the active is well absorbed but is released in the colon locally. Okay. Next question, can you talk further about the IP around the molecule or the prodrug technology and how long you expect market exclusivity on PALI-2108? Yeah, I think we had a slide on the patent is composition of matter. Patent life is to 2042. And so you would potentially expect regulatory exclusivity for the eight years and then potential for exclusivity through intellectual property protection to 2042. Excellent. So we've had great, great questions. I have one more question before we go to closing remarks. So you showed that slide where there's just a lot of activity, meaning acquisitions in the space. And there were some even at earlier stages, right? So we saw that on the slide. You're at an earlier stage, but you're progressing towards your first-in-human clinical study. What conversations, if any, have you had with pharma? Are you already having conversations? We are. Mitch, do you want to kind of talk about who we've talked to and kind of what their response has been so far? I don't know if I would go there. But yeah. But when we can say they've been enthusiastic, let's leave it there. But Mitch, do you want to talk about who we've met with so far? I mean, we've had initial discussions at major conferences, met with some of the big five-type pharma companies, and had initial discussions and sort of received positive feedback. I mean, the drug is an anti-inflammatory and an antifibrotic. The market is looking for oral drugs. Market clinicians, patients are looking for oral drugs, local drugs, non-systemic drugs, drugs with lower toxicity, drugs with improved safety profile, more efficacy. So I think it sort of checks all of those boxes. I mean, we've had KOLs, some that we work with, and others that are very high profile that sort of say, "This checks a lot of boxes." So yeah, we've certainly had a few conversations, and there is interest. Wonderful. Okay. So I just want to congratulate you both on a lot of progress. I think from the time that you have had the asset under your umbrella, we've just seen nothing but forward momentum and a lot of activity. You have a lean team, and we're seeing you work your way to your first-in-human clinical study. So congratulations on all of your work so far. Definitely an exciting time for Palisade Bio and a lot of opportunities for investors to continue to follow the company. J.D., before we close, anything you'd like to say before we end the session? Just on a personal note, I know many of the people who are listening to us today have friends or family or even personally may be afflicted by some of these diseases. And I can tell you, having several family members of my own that are going through this, it's a frustrating process, as Mitch was describing, to not know what is the best treatment and to know that whatever treatment you're going to get is going to have probably a one in five chance of working. And then you don't even know about it for three months, and then you have to start over again with a new therapy. The patients out there and the providers really need a better solution here. I'm excited that I think we're on the verge of providing one of those next-generation therapies for this important disease. Wonderful. That's great to hear for patients. It's great to hear for the scientific community and for your investors. So with that, this concludes our virtual investor closing bell featuring Palisade Bio. I want to extend a huge thank you to J.D. Finley and Mitch Jones for joining us today. I'd also like to thank our audience for your participation and great questions, as always. As a reminder, Palisade trades on NASDAQ under the ticker PALI. If you like what you saw today, I encourage you to visit palisadebio.com for more information on the company and to sign up to follow the company to receive their alerts as well as follow their social channels to stay current on the latest information. You can also visit virtualinvestorco.com for a replay of today's event as well as our latest segments and event calendar. Thanks again, gentlemen, and I wish everyone a great evening. Thanks, J.D.