Morning, and welcome everyone to the Jefferies Global Healthcare Conference. I'm Jordan Carey with the investment banking team, and it's my pleasure to introduce Puneet Dhillon, CEO of Skye Biosciences. Hey, thank you so much. All right, good morning, everyone. Yeah, thank you again for the invitation and being here at Jefferies. It's always a pleasure seeing the entire Jefferies team and talking about what we're working on at Skye. Today I'm going to go over with you first-in-class CB1 blocking antibody, Nemesimab, and I think it'll outline the presentation should outline how this is really this particular approach that we're taking does tap into this multi-billion dollar opportunity and highlights how the incretin class hasn't really achieved full, kind of complete resolve of obesity, and there's still a large unmet need. This is a differentiated antibody-based mechanism that we're working on, and it's coming out of a market that still needs safer, longer-term options. Before I begin, there is just the cautionary language. I'm going to be making some forward-looking statements, and I'll be covering today's presentation. We'll cover all the current data and kind of current assumptions that we're working with, but again, standard disclaimer, and encourage everybody to focus on the data. Also today, my colleagues in the audience, Dr. Chris Twitty, so we're available after this presentation to answer any questions. Our mission is to really pioneer and commercialize the first CB1 antibody to tackle the current and future unmet need in obesity. By 2035, half the U.S. adults may be obese, and GLP-1 drugs alone really don't cover all that demand because of tolerability, adherence, and overall cost issues. The takeaway here really is Nemesimab is designed to fill that gap that GLP-1 or incretins are really leaving behind. Even when you look at the Wegovy and Zepbound opportunity, there continues to be a significant amount of GI adverse events, lean mass loss. There's a very high discontinuation rate that continues to persist. Investors should really take note that over 30% of patients quit within four weeks, and about 40% of weight loss can also be attributed to lean mass loss. There continues to be a big demand for a therapy with better tolerability and a better body composition profile. This is a highlight from a JAMA paper that highlights that 2/3 of patients stop GLP-1 therapy within one year. That churn really directly translates into the provider and the patient frustration and opens up the door for more durable mechanisms. The durability side is really, you know, we would say is the commercial gold here, and that Nemesimab is really well positioned to capture that. CB1 is a very interesting pathway. It's certainly a non-incretin pathway, and what's important in this visual here is that we're targeting weight loss through a completely different peripheral-driven approach. CB1 is controlling energy balance, adipose-related metabolism, hepatic lipogenesis, and we'll walk through some of these anchoring components of the mechanism today. Crucially, peripheral CB1 drives weight loss without the central nervous system risks that have plagued this particular mechanism in the past. That's the key difference. The other important takeaway here is that this is a validated mechanism. When you look at what's actually the different mechanisms that have been used for weight loss, CB1 has been validated, but this is a fresh safety profile in terms of approaching it the way that we are with Nemesimab. Just to put it in context in terms of what we're referring to in terms of the validation that's taken place, there's really been what we would say meaningful weight loss proven by the class. Historically, rimonabant, which was the first-generation drug, hit about 3% placebo-adjusted at 16 weeks, and Novo recently announced their data last year in September, and it hit about 6%. The efficacy is real, and the hurdle has really been CNS-related safety. In both those cases, the first and second generation continue to highlight the risks of neuropsychiatric adverse events. When you look at it as a comparator to oral semaglutide, you can see that the efficacy numbers are really similar. Nemesimab is expected to keep the efficacy and remove the liability because we're staying out of the brain. Now, before I get into just the mechanism side, I just want to highlight a little bit of refinement that we've continued to do on the target product profile. We've recently concluded a pretty comprehensive interview of physicians, KOLs, endocrinologists, and there's three core use cases that really we can take away from that broad survey that we've done that this approach that we're developing addresses the monotherapy opportunity, addresses the maintenance opportunity, and it addresses the combo opportunity. When you think about those three core use cases, they really fall into the GLP-1 intolerant bucket, the GLP-1 non-responder bucket, or also an add-on or plateau or a combination therapy. Each one of these represents a multi-billion dollar slice in the market, and it's really an opportunity for a clear, clear validated commercial positioning for our drug. Okay, so let's dive into the antibody modality and why it matters. Just highlighting a couple of the attributes of this particular antibody. It is an engineered IgG4 antibody. We have half-life that we've shown about 18-21 days, which enables less frequent dosing, which is something we're continuing to evaluate. We have zero off-target GPCR binding. It's acting as a dual inverse agonist as well as a negative in terms of its approach and mechanism. It's a negative allosteric modulator. We've shown an NOAEL of over 75 mg per kg, which really gives us a vast safety window. The important takeaway here is that it's really best-in-class pharmacology. It's underpinning a really wide therapeutic window for us in terms of the way that this antibody has been engineered. Now, looking at the peripheral CB1 signaling, it's really a metabolic-focused target. Here, CB1 blockade is in adipose tissue, liver, kidney, GI tract. The idea here is really looking at this in a coordinated way, rewiring energy expenditure, insulin sensitivity, as well as looking at fibrotic pathways. I'm going to walk you through kind of each of these. First of all, just to set the groundwork in terms of I've made reference to staying out of the brain. This is some biodistribution data that shows superior brain exclusion. We've highlighted in three different NHP studies a really clean antibody-to-CSF ratio of under 0.02% in NHPs. There's also been a comprehensive amount of work done in clinical where we've done a phase I where we've showed zero neuropsychiatric adverse events. The images in the bottom right-hand corner are just showing PET scans showing no brain uptake as well. All right, so the first important kind of efficacy data here is in a DIO model. This is demonstrating a dose-dependent weight loss in a diet-induced obesity model. This is the first preclinical efficacy that we've shown of our mechanism in demonstrating a dose-dependent weight loss. What's kind of important here is that it's highlighting a very productive body composition with the emphasis on fat loss. In this deck, we have also highlighted repeat. I'm going to skip over that slide, but just the important thing here is that we've done these studies in independent CRO, and we've replicated the robustness and the reproducibility of that data. We've also highlighted now the kind of the validation of caloric reduction, which kind of indicates an independent pathway leading to this anorexogenic driver in weight loss, which is similar to what we see in the incretin class. That's one of the kind of anchoring components here in terms of the mechanism is that you are seeing a drive in weight loss, but now because we've been able to see the shift in caloric intake, we can also point to a completely different pathway driving anorexogenic pathway. Another way to look at this is how that additional anchor here is based on a really productive modulation in key hormones. GLP-1 is increasing with this pathway. We've also shown control of leptin, so we have control of hyperleptinemia, and the resistant levels are also shifting, which is really in a way all three of these highlight a coordinated or multimodal metabolic benefit. It's really a positive indicator on how this pathway is really starting to reshape broad metabolic parameters that are all linked to adipose tissue. We talked about weight loss, key hormones, modulation. There's another important anchor here in terms of glycemic control, which is where we've done this experiment both in a fasted—both of these were done in a fasted state, and we're showing improved fasted insulin and glucose tolerance, which really can highlight the broader cardiovascular upside of this mechanism. Finally, I'll touch on one important anchor that's kind of linked in two slides. This slide's showing Nemesimab's ability to really clean up the fatty liver in a dose as the dose increases. This is from our DIO model, and we've done pathologist-blinded scoring here in different H&E sections. What we've shown is a rapid dose-responsive decline in hepatic fat. We've also shown that in quantitative imaging, this corroborates with how the pathologist has read this as well. It's showing it's really a parallel fall in the steatosis area in both the score and the percentage area. In a kind of a related way, here is how we're showing improvement in obesity-related inflammation. This is the final kind of mechanism thing that we'll cover today, but it's highlighting how the mechanism is really driving lipolysis as well. Nemesimab has shown reduction in liver fat and improvement in adipose inflammation. This is really kind of another element of early data highlighting the shift in kind of the overall inflammatory markers that are important. And this is kind of the adjacent value that we think are important that highlight things beyond weight loss. As I stated, I'm going to skip over this because I've kind of indicated this was the caloric reduction. We're going to jump right into combination data that we've highlighted. This is the first DIO study that we did with Nemesimab and tirzepatide, which achieved 31.5% weight loss. This is really early data, but highlights the combination potential and that it could be additive. What's important to note here is that these are similar doses to the clinical dose in the case of Nemesimab and rimonabant. The rimonabant dose is close to the 20 mg dose, and in the tirzepatide dose, this is actually a suboptimal dose. The key thing here is we're still showing a really productive body composition, and this is a proof of concept for the additive combo strategy and really addresses a larger target addressable market. Now, switching just quickly to the potency side of the equation, this is highlighting the difference and similarity in two different assays and indicating about IC50 in both cyclic AMP and beta-arrestin assays that are highlighting that Nemesimab is equal to or better than Rimonabant without the challenges of any of the CNS risks. The important kind of differentiator here from a mechanism or the way that this is binding is highlighted by this quick animation. Unlike rimonabant, Nemesimab's potency really continues to show it's stable even when it's in about 40x endogenous ligand levels, which is really ensuring that the activity of the binding and the blocking of CB1 is happening even in obese physiology. It's a unique kind of receptor pharmacology that really widens what the efficacy window could be for this drug and allows us to bring on a lot more drug conceivably without having the challenges of any brain exposure, which is what we've seen in the case of rimonabant, where that's what the early clinical data from phase II highlighted is that they see a dose-dependent increase in brain exposure. All right, going into the more wider part of the story here, when you look at CB1 and specifically what we're doing in development, this is a very complementary pathway, and it's not competitive. We believe CB1 tackles energy expenditure and fat metabolism, and incretins are really tackling the appetite side of the equation. Investors should see the synergy of this. This is not cannibalizing the incretin market. This is hopefully plugging the gaps that we're seeing with the incretins. It supports the combo economics of this, not only from the commercial market, but also what the unmet need is from a patient perspective. We've set up all of the stuff that we've gone over in our mechanism side is obviously being evaluated in the clinical side. We're going to switch really quickly to the clinical side. There's a lot that's been done in the last 12 months. I've highlighted kind of the differentiation here in terms of the receptor engagement, how we're superior in terms of the exclusion from the brain. We are underway now in a phase II study that's called CBEYOND. This is a 120-patient study that's four arms, and it's divided up into Nemesimab versus placebo, as well as a combo with GLP-1. There is a placebo arm to that combo as well. Altogether, 120 patients, we're evaluating treatment at 26 weeks, followed by a follow-up. We have recently announced an extension of this, so we are allowing all of these patients that are enrolled in these different arms to cross over and continue a 26-week extension. I'll just highlight the schematic of that really briefly here is that in the combo arm, which is enrolling now, you finish the treatment, then if you're eligible, if you're within the four weeks from the last dose, you come into the extension. The monotherapy, it's the same approach, but you have a little bit longer follow-up period to widen the eligibility portion. After the second 26 weeks, we will still be doing a 13-week follow-up as well. The last point I'll make is just in terms of the upcoming important milestones. There's been a lot accomplished, as I noted in the last 12 months, where considerable effort has been put into launching this current CBEYOND phase II study. Now that study is coming to an important inflection where there's a data point later this year. We expect to have top-line data from that program in late Q3, early Q4. That gives us the first data point to go and speak to the regulators around the design of our phase II B. Meanwhile, the extension is going to be ongoing in the phase II A, and we'll have 52-week data in the first half of 2026. We are continuing to work in the background on all of our CMC and manufacturing. Like we kind of indicated, really well-positioned to become a fully integrated metabolic company. There have been kind of six pillars that we've been focused on, building on a very seasoned team of drug developers, really strong IP with Nemesimab, expanding our CMC and manufacturing, and including doing additional R&D on new formulation. We remain really strongly funded. We've raised about $107 million since August of 2023, and we still have a considerable amount of cash that takes us into Q1 of 2027. We are continuing to build on the advisory and other side to continue our development aggressively. Just to highlight the management team, Chris and I are here today at the conference, and other members of our team are kind of floating in different places this week. In our board, all experienced entrepreneurs, drug developers, over 40 different drugs and diagnostics that have been commercialized or they've contributed to commercialization amongst the entire team. Thank you very much.