Good morning, everyone. My name is Frank Tang, and I'm with the Investment Banking Division at Morgan Stanley. Before we get started, I'd like to read a quick disclaimer. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/research-disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, thank you all for joining us today for the fireside chat with Skye Bioscience. I'm joined today by CEO Puneet Arora. Puneet, for those of us who are not as familiar with Skye, can you give us an overview of where Skye sits today, your pipeline, and your priorities heading into 2026? Yeah, great. Thanks again for the invitation to Morgan Stanley. It's always a pleasure being at this conference and always very productive. We're in a phase 2 or mid-stage development in obesity, and we're developing a CB1 antibody that's a very exciting non-incretin target in terms of the space and the dialogue. Our discourse has been primarily dominated by the incretin class, GLP-1 or GLP-1 combinations. We are very excited about working on this validated pathway. This is a pathway that's been well observed to show dominance in terms of weight loss. In fact, there was a previous product approved. The second generation of class of drugs that have been in development, namely our antibody and then also these other peripherally restricted small molecules, have a really distinguished profile where they stay away outside of the brain. That's what we're excited about. We're developing that in a phase 2a, and that clinical readout is imminent. We've stated in terms of our guidance, late Q3, early Q4, with regards to that lead program. The other areas that OpEx is really focused on is lifecycle management of the lead assets. In that bucket falls into some of the other things we're working on in terms of broadening our IP. There's also kind of a parallel activity in terms of formulation where we're looking at improving our TPP. Right now, we're evaluating a weekly dose. We expect to be able to go to a monthly or less frequent dose. The third bucket is a very exciting kind of pipeline that continues to build on the antibody-based approach. We're excited about working on three buckets. Obviously, the clinical program is a dominant area of OpEx at the moment. Absolutely. The broad weight loss space continues to be pretty large and competitive. It'd be helpful if you can give us an overview of NEMAZENMEB and where that sits. Yeah, it's been really interesting to see how the world of focus on absolute weight loss has begun to shift to look at other aspects for sustainable long-term weight loss. We've been very active in discussions with our clinicians or just the overall physician community in the last year. In fact, we've done a very comprehensive survey of market access, and it's about 50 plus, about 60 different KOLs or physicians, primary care physicians, endocrinologists. It's revealed that just broadly, the broad statement is that obesity is very heterogeneous. It's not a one-drug-fits-all aspect. I know we know that the headlines that we hear in terms of the dominance of the marketed products have obviously shown a significant weight loss. However, there is still a need to address patients that come off of those drugs. There's a big issue here still that we're dealing with in terms of tolerability and discontinuation. For NEMAZENMEB, we feel we're really well positioned to fit into three broad categories. There is still a market there in terms of clearly a monotherapy opportunity. We expect that in the long-term weight loss, we should be in the double digits, and that is still an important competitive profile. The second area that is of really strong interest is the maintenance population. What's evident is that when patients are taking these incretin drugs, there is a large reason for discontinuation tied back to tolerability. Nausea, vomiting, diarrhea, these are issues that come up early, and patients are unable to take the drug through that period. Even so, even after they maybe force themselves through that process, there is a propensity to come off drugs. That could be for a variety of reasons. Unfortunately, you're going after a different pathway. Sometimes it's just a feeling of like wanting to get off the drug because they want their appetite back. The opportunity there is that we've seen based on real-world numbers is that about 70% of patients are discontinuing those drugs within the first year, let's say two years. There's a JAMA paper that actually was published that the 80% within two years. The challenge here is that in order to have a long-term sustainable weight loss, we do have to think about this over a more long-term chronic period in order to reestablish and reset and establish what that set point would be. That's where we think is a fascinating opportunity. What we've been saying is ours for the taking in terms of NEMAZENMEB really being able to come in, address the patient population that comes off of Zepbound or comes off of Wegovy in the frontline setting. There is a third exciting area, which is combination and the combination of an incretin with non-incretin. There's been evidence of that already with Caglizumab, with AMLIN, and GLP-1. We believe that the pathway that CB1 is addressing is very interesting and what's called orthogonal or distinct from the GLP-1 pathway that can be very meaningful. Right. Yeah, that's super exciting. Maybe as we dig into NEMAZENMEB a little bit more, could you give us an overview of the data that's been generated to date, as well as how you see it differentiating versus other therapeutics in development? Yeah, that's a great question. A bit loaded for us to get into all the details. We have had a really fantastic year of generating a whole bolus of different preclinical data that supports the different mechanisms. I can walk through a couple of the pillar components. First of all, what we're talking about in terms of development is a peripheral-driven mechanism, meaning that it's outside of the brain, outside of the blood-brain barrier, and essentially below the neck. We're looking for pathophysiology, physiologically looking at addressing these metabolic functions. If you take into account that obesity and overweight is a very complex disease where it is basically like this dysfunction that happens where the brain and these other hormones are not really doing their required job. The tissues, unfortunately, everything that's very coordinated is not really working properly. That's why it's called dysfunction. When fat is building up under the skin and starting to spill over into these other organs and inflammation and other aspects, what we're trying to do is counteract that. With CB1, by the peripheral mechanism, we're focused on specific mechanisms that really help counteract that. Key among that is still this idea of caloric restriction or regulating appetite, regulating hormones. I think it's a bit of a misnomer that CB1 isn't doing that. What we've now been able to establish based on preclinical data is that really strong evidence of being able to actually regulate and modulate these appetite-regulating hormones. We can see that leptin and GLP-1 are influenced. Leptin's coming down, GLP-1 is being increased. That's actually really nice to see relative to the GLP-1 class. The second important pillar there is looking at glucose regulation and overall kind of reestablishing that homeostasis that we expect in the body. Key among that is when you have these high levels of insulin, unfortunately, it signals to store fat. What we're trying to do is bring back the sensitivity to insulin and bring back the kind of rewind that resistance that's built up because of insulin. The third area that we've been able to establish really strong evidence, and this has all been repeated now, is in lipid metabolism. When you see this fat kind of spill over into other organs, like let's look at the liver, you can now then start to see fatty liver and other things. We've been able to show that we've been able to bring down cholesterol-related markers or other lipid-based markers and actually bring down that fat. There's been really good evidence of lipid metabolism. That's an important kind of underpinning in terms of this comment that's often made between lean mass preservation and fat focus. CB1 is certainly a pathway that's biased towards the fat pathway. The fourth remark I'll make is just around inflammation and fibrosis. It's again another distinct mechanism, and we've shown now evidence with different markers regarding inflammation and fibrosis. I mean, that's a lot of continuous exploration of the mechanism. You've obviously disclosed that you expect top-line data from your trial later this year. How would you guide investors to view as the bar for success? Yeah, that's an excellent question and something that we continue to wrestle with on a continuous basis. When we designed the trial, we didn't really have a really clear number to just pull out of it. I mean, rimonabant was there, but it was a different approach to the CB1 pathway being a small molecule. The opportunity with NEMAZENMEB is that we think there's a really distinct competitive profile relative to the small molecule. We feel that we have a really good mechanism there that can drive the required inhibition and antagonism to have this weight loss in the periphery. What we recently guided towards is 5% to 8% top line at 26 weeks. We feel very confident about that now that we've seen some new evidence from peripheral-driven CB1 approaches, namely MOLNUNIBANT. If you recall, MOLNUNIBANT finished a phase 2a and reported at 16 weeks 5.7% adjusted weight loss. We feel that the 5% to 8% in this proof of concept study should be achievable. What we're really looking for is a really clear separation between the placebo and the active arms, and that this is our minimum for proof of concept success. There's also another scenario here in terms of 8% or more in terms of the high end of the proof of concept outcome, but that's what we're looking at in monotherapy. There's a caveat to that in terms of the kinetic profile and how fast that weight loss is expected at 26 weeks versus 52 weeks. Last week during our KOL call, the KOLs that were on the call actually pointed towards that. It was maybe well supported based on some preclinical evidence. In fact, last week we reported a favorable comparison against MOLNUNIBANT where we looked at three different doses of NEMAZENMEB when compared to the therapeutic dose of MOLNUNIBANT. In all three of those doses, NEMAZENMEB actually showed a really favorable weight loss profile to MOLNUNIBANT. What was interesting is the beginning part of the drop in the weight was a little bit steeper right off the bat with MOLNUNIBANT, and then it tailed off. When we've spoken about this internally and R&D has kind of pointed to is that this may be a component of central engagement that's coming into play. That's why we might see an earlier drop in terms of weight loss with the small molecules. Keep in mind, we want to avoid central exposure, and this has been the challenge with the small molecules. What I'm pointing to is the kinetic profile that we're watching for. We want to see what that curve, the trajectory of the curve at 26 weeks, is really important. The second part of your question is the combination. The combination side is really compelling. There's unfortunately no precedent between CB1 and GLP-1 combo, but what we've been extrapolating is we want to definitely see additive weight loss. There's now really strong preclinical evidence that we've seen in a dose-dependent manner of a very additive or in some cases a synergistic weight loss. What we've been stating there is what we'd like to see is 10% or more. Recently, when the KOL call happened, that was kind of the consensus amongst the KOLs as well, that the profile points towards this additive weight loss based on the evidence to date. Obviously, one of the key things we're also watching for in that combination is whether there's any additive tolerability, which we want to avoid, or any GI disturbance we want to avoid. This is, again, where we think we have the upper hand to be able to really minimize any extra GI disturbance because it's a different pathway. Yeah, absolutely. Before we dig a little bit more into combo, I'd like to maybe go back a little bit and focus on CB1 as a target. Neuropsych, obviously, safety is viewed as incredibly important for this target. I would love to kind of talk about what other safety measures or metrics are you hoping to kind of see to differentiate NEMAZENMEB? Yeah, you touched on a really important cloud that's been in this class. It goes back to the rimonabant days where it certainly was a very important issue that pulled that drug off the market. In some ways, when we look at this broad area of anti-obesity medications, it seems like the goalposts have also shifted a bit because now you look at GLP-1s and they also have this concern of some neuropsychiatric adverse events. With CB1, I think there's very little room for error. Unfortunately, with the small molecule, the second generation of small molecules, which were designed to avoid this, they have also shown that they haven't escaped that issue yet. Especially what I'm pointing to is the MOLNUNIBANT data where it was pointed out that they saw in a dose-dependent manner these adverse event profile or adverse event effects. With the evidence with NEMAZENMEB, we feel we have really established a benchmark in terms of neuropsychiatric safety or overall safety regarding neuropsychiatric concerns. That's based on this really strong distribution data that we have, the biodistribution data that we've shown in multiple non-human primate studies. We've also conducted a phase one where we saw zero neuropsychiatric adverse events. In the current trial, we've built out a really robust profile of questionnaires and other patient information that we're collecting. We've also had a safety committee involved in evaluating the study on a quarterly basis, which is done on an unblinded basis with the safety committee. We've gone through four of those now. I think we're operating with an abundance of caution. We believe that the requirement of the uptake in the market in the commercial setting is that we don't have any room for error on the neuropsychiatric concern. That's great to hear about the differentiation. Going back to the combo therapy potential of NEMAZENMEB, you mentioned that there was some data that was generated. Maybe if you can give us an overview of the preclinical data and what you saw there. Yeah, there's been a really comprehensive amount of work done. This goes back to 2024 where we built out a human CB1 knock-in model. Even though CB1 is a pathway, CB1 is a conserved pathway, the antibody is not cross-reactive to, it's only cross-reactive to humans. We've had to build out a human CB1 knock-in and a myriad model. That has been a very important kind of milestone in itself because it helped us continue to build a really steady cadence of data, going early to the first monotherapy data and then now recently several repeat studies on the combo. The data that we announced last week pointed towards our second important study looking at three important questions that we've been evaluating in combo. One is what is the amount of the degree of weight loss we can see with the best-in-class GLP-1? We looked at the combo with tirzepatide, which is a GLP-1 GIP, and we saw a 46.6% drop in weight in the study. The second question that we have been evaluating is what is the degree of rebound when you compare in these DIO models when the cohorts come off of tirzepatide or an incretin versus when they come off NEMAZENMEB. There we saw that in the tirzepatide cohort, there was about a 29.7% rebound effect, 30% rebound effect, whereas in NEMAZENMEB, the rebound was only about 7.8%. This is based on discontinuing drug and evaluating. This is all accelerated. These DIO models are kind of mimicking about 100 weeks in human lifetime. It really gives you a good glimpse of what's possible in terms of the biology. The third question that we're looking at is, instead of just coming off the drug, what if you give these cohorts NEMAZENMEB? Can you blunt the rebound effect? There we saw that when that tirzepatide cohort was given NEMAZENMEB at that discontinuing, so we switched over to NEMAZENMEB, we were able to bring down that rebound profile to only 13%, 12.8% versus the 30%. It really points to this different pathway. The 47% drop and this rebound, it just shows how the caloric restriction pathway is only one aspect of it. Clearly now with CB1, it's pointing towards these other mechanisms that we talked about, like lipid metabolism, glucose regulation, other things. Now we're continuing to harvest that data for looking at highlighting some other important biomarkers like that from the combo as well. We look forward to sharing more of that. I guess it'd be beyond sharing additional data on that as well. What are some key takeaways in how you would inform your forward plans with this promising weight loss and rebound? The purpose of all of these preclinical studies has been kind of twofold. One is looking at and understanding the mechanism and just being clear in terms of what our mechanism is and the pathway that we're going after versus the incretins, as well as even when you compare it to the CB1 small molecule. That's been one, is understanding that biology. The second has been how it supports our product profile. There is a, like I said earlier, there's been a fair amount of work that we've done. We've always put the target product profile at the front, at the forefront of our development decision-making. From day one, we've recognized that the dominance of the market has been in the incretins. There's a very large pipeline. Nobody can deny that there's plenty of choices. We recognize that with those GLP-1 pipeline, all of those different drugs are only pointing towards some incremental improvements in terms of maybe they take a little longer to work. Maybe they have a bit of improvement in tolerability profile. Maybe they're an oral versus an injectable. That is not enough in terms of thinking about tackling this therapeutic area. This is one of the most fascinating areas of a study where we can have a long-term improvement in terms of metabolic health. That is a lot of things that are happening. You know, this is tackling one disease that encompasses many, many other comorbidities as well. This is where I think the evidence that we've been able to generate on the preclinical side is really helping to support that broader application in some of the comorbidities. For instance, when we're looking at lipid metabolism, we now have really good evidence of steatosis and showing improvement in steatosis with our mechanism. This is directly correlated to liver and NASH. We have previously done a bit of work in the chronic kidney disease area, and we're looking forward to continuing to explore that. We've also explored some other interesting rare disease indications that are also linked to obesity. For us, the preclinical evidence is one is build on the obesity profile, but also position NEMAZENMEB as a broader franchise in terms of there's really more. It's one fascinating molecule and pathway that can address a really wide range of diseases. That's very helpful. Moving beyond maybe just that program for a little bit, you obviously have a robust R&D program. What other potential do you see in utilizing your expertise in CB1? Yeah, so our CB1 pathway actually, our CB1 understanding does stem for quite some time because we looked at CB1 in another indication as well before. For us, the future is around CB1 inhibition as an antibody and building on that backbone. If you asked us a year ago, we said, you know, it's building on a GLP-1 kind of backbone in terms of that's what the market is. We think we're there in terms of being able to really support a really strong set of data to be able to combine. If there's interest out there from a development standpoint, we've been very open-minded about the opportunities to combine with the current format of drugs. We have semaglutide, we have tirzepatide, we have others that are in development easily. We are pretty agnostic to combination. For us, the future is how that can evolve into a unimolecular drug. The antibody does give us a lot of flexibility to do that. We won't go into some or all of those targets. I'll just save that for the next conference. We're definitely excited about the potential of being able to combine. That's where the fascinating thing about this area is that imagine a product that you can take once a month or once a quarter, and it's tolerable, and it's supporting broader metabolic health. That's what we believe is the future of the AOM space. I mean, what's happened in the last two years is just absolutely mind-blowing in terms of the amount of research and how much the energy and the resources that have come into this area of research. We couldn't be feeling like we're in a better place from a therapeutic area. This is one of the most exciting therapeutic areas that we've ever worked on as a team. Absolutely. We'll look forward to learning more about that. Moving on to the corporate side of things, could you give us an overview of your cash balance in some way? Yeah, so we've reported as of June 30th, $48 million and change. We have continued to be consistent with our cash guidance. At the moment, we have cash until Q1 of 2027 is what we've stated as our guidance. What that means is that we are continuing to have our foot on the gas pedal in terms of development. We are obviously moving really quickly in terms of execution on our phase 2a study. We just recently announced the completion of enrollment on the extension study. This is the next 26-week portion of our study. We'll have 52-week data. This is a decision we made in Q1, and we reported that in our Q1 earnings call. There has been a focused effort to continue to develop the data or generate the data to support our development decisions. The next development objective here is to launch a phase 2b study. The purpose of the phase 2b study is to have an understanding of the dose, the maximum effective dose, and also look at dose frequency. Perhaps we can bring that frequency down, make it less frequent, so maybe towards a monthly dose is something we're evaluating. Those are decisions that are important for our phase 3, and this next study allows us to do that. Coming to our cash, the cash has been deployed in a very kind of systematic manner to support all of our development decisions, continue the lifecycle management. Things like formulation and the other comment around the pipeline, we have a little bit of effort there. I think we have done a stellar job on the G&A side. We've kept our G&A very low. It's always interesting when we start comparing. Overall, I think we've been running a very efficient shop. That's great. Investors always appreciate the discipline. Yeah, definitely. To close things out, maybe if you can leave us with the most important milestones and updates that you would like investors to focus on for the remainder of the year and the next 12 months. Thank you again for the opportunity to highlight everything that we're working on. There's always a lot to cover. In terms of coming up, there's a very important kind of inflection point regarding the top line data. That is something that I think all eyes are focused on at the moment. Certainly, internally, that's the focus. We have been, I think, doing a very comprehensive job of highlighting what to expect. There's a lot of information that we put out last week on a KOL call regarding specifically that program. Top line data, late Q3, early Q4. The next important milestone is related to the development decisions around phase 2b. We will be communicating that post-data. We continue to generate this broader preclinical evidence based on the work that we've been doing. Some of that next preclinical evidence that we look forward to sharing is pipeline-driven. I think we've done an excellent job of building out support for what to expect on the clinical side of the current program. We can now, I think, shift to other things that we're looking at. That's in the buckets of the milestones. It's going to be an exciting year for us. This 2025 has been important to really demonstrate the proof of concept. The rubber continues to hit the road in terms of how fast things are moving now. The stakes continue to get higher. Now, as a mid-stage development company, I think we are a very interesting profile relative to the peer group. Right, right. Very exciting next 12 months for you. That's all the questions I have. I'd like to thank everyone for joining us today and look forward to our next conversation. Thanks, Frank. Yeah, appreciate it.