Good morning everybody, and welcome to the Morgan Stanley Healthcare Conference. Very pleased to have on the stage Gary Glick, CEO of Odyssey Therapeutics. Before I kick off, just a few important notes. Please see the Morgan Stanley research disclosure website www.morganstanley.com/researchdisclosures, and if you have any questions, please reach out to your Morgan Stanley sales representative. I was very concerned about finding this disclosure language, and now that that's out of the way, we can kick it off. Perfect. Gary, great to have you. Actually, I think this is the first time we're hosting you as a public company CEO at the Morgan Stanley Healthcare Conference. You've had a long history in both biotech and academia before you moved on to the private side. Can you give the audience just a little bit of background on what led to you founding Odyssey and what was the sort of gap, either from a scientific or medical standpoint, that you were looking to fill and are looking to fill? Well first, good morning and thank you for the introduction. Good to see you again. I've been working in inflammation and autoimmunity I think since 1990 when I started my faculty position and over the course of a number of different companies, and I've watched the sort of the space evolve over I guess close to 40 years now. Despite the fact that there's been, I think, advances across the field in making immunomodulators for a variety of different conditions, one of the things that really is still standing out for patients is the ability to treat large numbers of patients, put patients into deep, long-lasting remission, and to do so in a very durable way. Odyssey was set up to capitalize on novel insights in biology I think that's emerged over the last 15 or 20 years that has significant potential to achieve all of those goals. Okay. This is the first company that you've brought to the public market out of the many that you've founded and been involved in. What was the thinking behind that and, I guess why does Odyssey need to be public whereas some of your other endeavors were a little different? It's true that seven of my last companies were all sold to large pharma. Most of those organizations were one asset or two asset companies. One of the things that I wanted to be able to do different at Odyssey was to be able to work across a larger portfolio of medicines and to work in different modalities. There's exciting things in small molecules. There's very exciting developments in biologics. I think the ability to work on both of those in one organization is one of the visions that we had for Odyssey when it was established. Really the only way to finance an organization like that is in the public markets. Okay. Let's move on to OD-001. You'll probably have a nickname, and RIPK2. IBD has become, I think, increasingly interesting, but also there's a lot happening from a development standpoint. RIPK2 may be not as advanced today as some of the other sort of mechanisms. What is it about RIPK2 that you saw an opportunity either from a biological or scientific standpoint within UC? Yeah. Maybe let's start with the overlying medical question because that's really important in how we think of everything at Odyssey. I'll start with a personal story and maybe go into a little bit broader. My son, who's now 31, was diagnosed with Crohn's disease when he was 13. I watched him go from REMICADE to HUMIRA to SKYRIZI, and now he's looking for his fourth medicine. I think the journey, his name is Jeremy, that Jeremy has sort of gone on over the last 17 or so years is characteristic of many patients with inflammatory bowel disease. Medicines may put them into symptomatic remission. That remission is usually short-lived, and then they have to go onto another medicine, and that second medicine is usually much harder to put them into remission. Oftentimes they'll lose response there and go onto a third and sort of a fourth. That is really kind of the big picture we're trying to address. RIPK2 is a target in the innate immune system. It recognizes bacteria that translocate when the epithelial barrier is breached, and it really starts the inflammatory process in inflammatory bowel disease. It has the chance to block, if you will, the root cause of inflammation and turn off multiple downstream cytokines and effector molecules rather than target any one specific inflammatory pathway. That's important because we know that inflammatory bowel disease is caused by multiple cytokines, multiple chemokines, multiple inflammatory mediators. If you could kind of turn all of them off at once, you have the potential for a broader therapeutic response, deeper remission, and more long-lasting remission. I guess if it's such an intriguing and obviously sort of broad-reaching target, why has nobody else done it and how do you drug RIPK2 successfully? Good question. The target was discovered in the early 2000s at the University of Michigan where I actually was on the faculty and I knew the inventor of the molecule or the inventor of the target. His name is Gabriel Nuñez in the pathology department. It took a better part of 18 years to actually understand the biology that led from RIPK2 activation to the production of inflammatory cytokines. We now understand that in order for that to occur, there needs to be binding to RIPK2 of a second protein known as XIAP. When XIAP binds to RIPK2, it activates the protein, leading to the production of things like TL1A, TNF, and IL-23. That discovery really only was made and published around 2018, and in pharma years, that's yesterday. It takes time to understand that biology and translate that into a small molecule understanding. The ability to block two proteins coming together is among the harder problems in medicinal chemistry and drug development, and we're very fortunate at Odyssey to really have an outstanding team of chemists and biologists that were able to put together the right set of assays and the right chemical matter to do that, and do so in a very safe and effective manner. Okay, perfect. Moving on to beyond the science and into the clinic. You have reported your first proof of concept data for OD-001. Maybe just a few highlights of that data and what stood out to you in terms of connecting the results you are seeing with the biology that you have described? So just to take a step back for a second, we conducted an open-label phase IIa study, where 41 patients completed a higher dose, and now 15 patients have completed a lower dose. We reported top-line results of a 27% clinical remission. One of the interesting things about the trial was not only are the remission rates we are seeing for induction very similar to what one sees in today's advanced therapies, but all of the data across the board is completely concordant. So we are seeing good reductions in inflammation histologically, endoscopically, and perhaps most important, we do not see a diminution of activity when looking at patients that have seen prior advanced therapies. This is really a big problem in inflammatory bowel disease. As I mentioned earlier, taking you through my son's journey, patients that fail, after they fail a particular therapy, it is much harder to put them into remission on a second therapy or a third therapy. Virtually all of the marketed therapies that we are familiar with, and ones that are in development, all lose significant activity. RIPK2, on the other hand, patients that have seen one or two therapies, they do not lose activity relative to patients that have been naive to advanced therapies, which is a very important differentiation point. From a biology standpoint, we believe we understand that because the cells that drive resistance are the target cells of RIPK2. Again, RIPK2 is the first protein target in the innate immune system that is going forward in the clinic for inflammatory bowel disease. By taking advantage of this target and the biology, we are able to achieve things that you simply can't achieve with any individual anti-cytokine therapy, as an example. Was there anything, in reviewing that, as you said, very impressive first data set, the fact that you were able to see responses in refractory patients that had been on advanced therapies, was there anything else that stood out to you that sort of increases your confidence moving into later stage development? A number of different things I think give us very strong confidence in the data that we see and moving forward in a robust way. First, as I mentioned, all of the data that we see is concordant, whether we're looking at biomarker data, fecal calprotectin data, histology data, endoscopic improvement, or the clinical remission data, everything falls in line. From a patient standpoint and a development standpoint, one of the important things for patients is a rapid response. People want to stay on drugs that are working, and the rate of response that we're seeing, looking at rectal bleeding as an example, is very similar to what you see with RINVOQ upadacitinib. So within a couple of weeks, patients start to feel good, and that differentiates from most of the biologics, where it takes usually multiple weeks, if not months, before you start to see improvements. That was pretty exciting. You have a great setup into later developments. But I think as I'd alluded to in the outset, there's a pretty fulsome pipeline in development across the mechanism target, maybe some of the usual suspects. But as you look at OD-001's positioning over the next 5-10 years, we're seeing bispecifics, combination therapies, some other sort of novel late-stage orals. In your mind, where does IBD go in terms of are we going to see combination treatments? Are we going to see expansion due to orals? What is your view of how the market evolves over the next 5-10 years as you come to market? You are right, there's a lot of activity in inflammatory bowel disease, which is, again, great for patients. I think we have to start with what is the North Star that the patients need? That is higher remission rates, deeper remissions, and more durable remissions. By deeper, I mean true histologic healing. If you start to think about trying to come up with a therapy that really hits all three of these, and maybe perhaps on top of that, convenient for patients, that should not be underestimated. It's having, for example, an oral therapy, which patients can easily take during the day, the morning, is very important for their lifestyles and for their daily wellbeing. I think RIPK2 is very unique there. Again, it has the potential to turn off the immune response early, lead to more durable remissions, and to deeper remissions because you're blocking, if you will, the smoldering inflammation that's constantly present, even when patients are, quote, "in remission" on a biologic. From a combination standpoint, it's completely orthogonal to every other mechanism that's being tested. That's very important from not only an efficacy standpoint, because it gets you a completely different arm of the immune system to attack, so you're kind of working up a ladder and walking down the ladder versus going down the same sort of rungs together. It's also important from safety. From an immunosuppression standpoint, RIPK2 would only be anticipated to lead to a modest increase in mycobacterial infection, which is very different than a number of the biologics. Then, some practical thinking about biologics. If one is combining two mechanisms that patients have seen before, it's quite possible that a patient may have failed one of those mechanisms. How does one ethically put a patient on, let's say, an alpha-4 beta-7, IL-23, where the patient may have failed the IL-23? Is one really expecting to see more activity there? Is a payer going to pay for that? Then if the patient actually fails that, you're now sitting with perhaps two half-life extended antibodies where the patient is not doing well. How do you add a third potentially immunosuppressive agent on top of that? I think having where RIPK2 positions across all of those is unique and I think sets it up for success and really is a backbone, if you will, toward a number of different combinations. Maybe we come back to the combo opportunity specifically for OD-001. So you've announced plans to study OD-001 in combination with, I'm going to say ENTYVIO because I can't pronounce the alternative. Vedolizumab? Yes, there we go. I think you've sort of touched upon it in terms of this being orthogonal to everything else that is out there. Why choose that combination, and any plans to look at other combinations beyond ENTYVIO? It's a great question. First, the preclinical models of inflammatory bowel disease are really not predictive of efficacy in the clinic or even how to compare compounds. This has to be one that's sort of science and empirically driven. We know that ENTYVIO is the standard of care for patients right now that have ulcerative colitis, so we're dealing with a medicine that is very well known to physicians. Physicians have used ENTYVIO off-label and feel very comfortable with its safety, in combinations off-label, so they're very comfortable with the safety. Safety is very important when one are combining a novel mechanism with a standard of care. Then third, as you mentioned, it's completely orthogonal. It is the most adaptive, if you will, of the adaptive immune therapies because it blocks the trafficking of pathogenic T cells into the gut. Again, thinking about working from the bottom up, turning off the root cause of inflammation, top down, blocking pathogenic T cells from entering the gut, releasing more cytokines to cause more tissue damage, I think gives us the best chance for a safe and powerfully effective combination. Perfect. Let's move on to what comes next, and then I do want to have some time to touch on the rest of the pipeline, which was a key reason for going public. In terms of upcoming clinical studies, you've said that you expect to initiate 2 clinical trials later this year, a monotherapy phase II-B. We've talked about the II-A combination study, and you will be providing an update probably at some point this quarter or next quarter, but is there anything else you can share today in terms of the design and the outlook for those studies? The study for the combination study with ENTYVIO will be presented at the ACG conference in Nashville by Dr. Bruce Sands in a couple of weeks. We will learn more about that, and I think that will be viewed as a very robust trial to really determine efficacy and the level of efficacy in combination. As you mentioned, we haven't provided guidance yet on the design of the monotherapy. One should expect that to be coming. In addition to that, at UEG, Bruce Sands will present more of the data, if you will, that came out of the II-A study, and we will be providing a more robust update on a number of exploratory biomarkers and different data cuts at a company presentation following his presentation. Perfect. Last one on OD-001. Beyond the updates, obviously the study initiations, the UEG presentation through 2027, what more should we look out for from OD-001? Yeah. I think, again, starting with the UEG presentation next month, we will be looking, I think, the exploratory biomarkers. We have very comprehensive transcriptomic analysis of patients prior to starting therapy in advance and after therapy. With that, looking at changes in fibrosis genes, inflammatory genes, differential cell populations, I think will be very informative as to the mechanism and the robustness of the mechanism of the drug. In addition, seven additional patients from the low dose cohort will be presented and will provide, I think, a feeling on the dose response nature of the drug. At the end of 2027, both the monotherapy and the combination therapy will read out. We will have really three different clinical presentations within the next 14 months or so. On OD-001? On OD-001. Yes. Perfect. Maybe we switch tack and move on to the next one, OD-002, SLC15A4, which is a bit of a mouthful. You have planned to file a CTA. Tell us about the target, the program, why an oral, what is going to be exciting here? Yeah. To look out for? Folks have been familiar with the role of interferon in diseases like lupus, other interferonopathies, obviously the role of B cells in mediating things like IgA nephropathy, lupus nephritis. The SLC15A4 pathway, if you will, is instrumental in leading to the production of pathogenic interferon through a transcription factor known as IRF5. It is also critical in the expansion and maturation of pathogenic B cells, known as age-associated B cells, that drive diseases like lupus and Sjögren's and myositis, and even IgA nephropathy. In many autoimmune diseases, and in fact, a number of chronic inflammatory diseases, this pathway begins when what are known as toll-like receptors, in this case, either toll-like receptor 7, 8, or 9, becomes activated with nucleic acids. That signals the activation of SLC15A4, which is ultimately responsible for activating IRF5 and kicking off this pathway. By blocking SLC15A4, which the biology is newer here, it is about seven or eight years old, it gives you the chance to very, very selectively and effectively block the IRF5 transcription factor pathway. Again, prevent the maturation and proliferation of pathogenic B cells and block the production of interferon. We are very excited about this target, given the breadth of opportunities that it can go in as monotherapy. You could even think about this as a combination, as maintenance therapy for other B-cell depleting therapies. It is a very exciting target, and we anticipate being the first in the clinic. It is a very hot field with a lot of competition. Anything you can or want to say around timing for that at this point? We plan on filing the CTA this year, which folks can probably figure out when the phase I studies would start. I think one of the important things to keep in mind about this, particularly as we think about catalysts and also what to look for in the next 12 months, is that sort of ex vivo stimulation assays in phase I for interferon have predicted phase II outcomes. At the end of phase I, we should have similar type of data and one could sort of read through there. Because you are first in the clinic with this target, you sort of touched upon some other parts of the pathway in terms of B -cell depletion that you touch upon. Are there any, in your mind, helpful or relevant analogs? I think we have seen some validation of TLR7 and TLR8 very recently. Yeah. Is this related, how closely related, IRF5 as well? Yeah. Just anything helpful just to orientate. Maybe to start with the biology, there is very strong genetic validation of TLR7 and TLR8 and the role of TLR9 in lupus and other interferonopathies and other diseases. BioLineRx. Yeah. Which reported positive data, I believe last week, with the molecule they licensed from Bristol Myers, Merck, and others, Merck KGaA, and others have reported positive data here on the 7s and 8s. Because seven and eight directly signaled through TLR, through SLC15A4, one sort of has sort of a formal, if you will, proof of concept based on those studies. What those molecules do not do is pick up or block signaling through TLR9, which is important for the response to extracellular DNA and the production of pathogenic autoantibodies. For example, lupus anti-double-stranded autoantibodies come via the TLR9 pathway. A number of diseases, even cutaneous lupus, has a component of TLR9. We should be able to pick up all the activity that the 7s and 8s get, plus the added benefit of nine. And just in terms of development, and again, may be too early, but is this more likely to be lupus-led, given the biology, baskets, or TBD? The strategy is really to take advantage of cutaneous lupus for the most expeditious proof of concept, and it also gives us access to skin for mechanistic biopsies and the like. And then to think about development really in a basket form, because there's so many different opportunities, and really let the human biology guide what is going to be first, second, and third. Perfect. Okay. So we've done OD-001, OD-002, but there's more. And you have some biologics as well on some very interesting targets. So beyond what we've covered, what else are you working on that's going to be exciting? Obviously, some of it is public domain. Maybe you can sort of share some insights? Sure. Beyond that as well. One of the kind of common themes throughout everything we work on at Odyssey is to try and work on upstream targets that have the potential to turn off broad responses, what are often pleiotropic immune responses. It is also correct that, as I talked about in the beginning, we wanted the ability internally, because all of our molecules are discovered internally, is to have a robust biologics capability. One of the first targets that we looked at in immunology there was a target known as TNFR2. This is tumor necrosis factor receptor 2 expressed on effector T cells. One activates TNFR2, one leads to the production of regulatory T cells. Unlike regulatory T cells produced with low dose interleukin-2, which has shown some clinical benefit, there are a number of problems that one finds via the IL-2 pathway. The cells that are produced, if you will, via TNFR2 are a much higher quality cell. They persist much longer. They have a much higher immunosuppressive level of function. They get to tissues much better, and they are able to actually start repair programs and activate certain transcription factors that do not show up down the IL-2 pathway. There is almost no condition you can think about that a robust regulatory T-cell could not address. We are very excited about this program. As we have guided, it is in GLP toxicology, and we are excited about moving this forward. Excellent. Anything else that you think is not appreciated in terms of the platform or the pipeline? OD-004, I will just stop at OD-004. Yeah, we'll have to stop at OD-004. I'll just say something maybe about the platform. OD-004 is a bispecific molecule that targets both TSLP and IL-33. As you may know, IL-33 has recently become validated through the AstraZeneca work with tozorakimab. The Odyssey IL-33 component of this bispecific phenocopies tozorakimab. It's a very potent and highly selective molecule that essentially has the same properties as toza, and our TSLP piece is among the most potent TSLPs that I think has been reported. What's unique about this combination is that human genetics, and we spend a lot of time with the UK Biobank, is predicted to be synergistic, and we're very interested in taking this forward for non-type two respiratory diseases. Synergistic as opposed to purely cooperative. Truly synergistic. Interesting. It has gotten a lot of excitement externally. The platform at Odyssey is really a combination of a series of experimental and computational technologies that allow us to move very rapidly. For example, the OD-002 program, that started with a virtual screen in October of 2024 and finished GLP toxicology in under two years. The OD-001 program, the company didn't exist in September of 2021. There was a bank account. We finished phase I studies in 2.5 years from setting up the company and discovery. Not all programs move that fast, but we have the ability to move a number of them at that speed, which is obviously very important from a competitive standpoint, from a capital efficiency standpoint, and the ability to continuously innovate and have a robust pipeline. You're a young company. You'll have several readouts, two very important ones for OD-001 by the end of next year, another CTA, and sort of more coming behind, and you're public. What is your vision for Odyssey 5-10 years out? Is this we do everything ourselves? We build all the way to the market? It depends? I mean, what does success look like from your standpoint? Yes. Yes. We're very- It's a good question. We are very fortunate that my former colleague and friend and mentor, Jeff Leiden, chairs the board. We have a very experienced board of operators that have done everything from target discovery to obviously commercialize some of the most important medicines that exist today, helping guiding the company. Ultimately, we envision that Odyssey, when appropriate and for the right medicines and the right indications, will commercialize drugs ourselves. We would ultimately obviously like to work with partners where appropriate to commercialize in indications that just does not make sense for Odyssey. But I think the ability to continue this cycle of discovery, rapid innovation in novel but reasonably de-risked areas to produce high impact medicines that change people's lives is what I would like to see the company continuing to do as we push forward for the next 5-10 years. Actually, we have five minutes, but I am actually going to let Gary go because I think we have covered everything I needed to cover, and if there is any sidebar questions from the audience. Thank you once again. It has been a pleasure. Super exciting. Thank you. By next year, we will have even more to talk about, so that is great. Thank you everybody for attending as well. Good to see you again. Thank you.