Odyssey Therapeutics, Inc. Common Stock Stifel 2026 Virtual Immunology and Inflammation Forum

Well, thank you, Alex, and thank you to Stifel for having us on the fireside today. I am Collin Todd, Head of Strategy and Business Development for Odyssey. Odyssey was founded in 2021 with the idea of delivering transformative therapeutics to patients that are suffering from autoimmune and inflammatory disease. Today, we will obviously discuss several of our pipeline programs and upcoming catalysts, but I think first it is good to touch on some of the organizing principles of how we put the company together. First, all of our programs are homegrown. Everything that we are working on are things that we have started since 2021. Second is that we are using two validated modalities to advance our portfolio, small molecules and protein therapeutics. Then the third is ultimately our goal is to, for medicines that we advance, to be the first or second to the market.

Yeah. First, I think it is important to note that all of IBD starts with the breakdown of the epithelial barrier. In this case, when the gut barrier is broken, the bacteria that are present in all of our GI tracts ultimately becomes exposed to the host immune system, and in doing so, it sets off the downstream inflammatory cascade. This is something that we have seen, RIPK2 ubiquitination, both in patients with ulcerative colitis as well as Crohn's disease. This is something that we see as ultimately being applicable to all patients within the inflammatory bowel disease space. With respect to genetic rationale, there are different mutations that are related to RIPK2 sensitivity or activation. These include CARD9 and ATG16L1.

Both of these ultimately increase the risk of patients developing inflammatory bowel disease. We think supports the concept using human genetics of going after this target.

Yeah. I think first you really have to start with the biology that you're looking to block. Many of the first-generation approaches going after RIPK2 were targeting the RIPK2 kinase function. It was back in 2018 that there was a definitive series of papers that actually illustrated that the kinase function was not necessary for downstream signaling activity. What was actually important was the scaffolding function. From the very start of when we worked on this program, we set out to create a RIPK2 scaffolding inhibitor. What our molecule does is it binds to RIPK2 and holds RIPK2 in a conformation that reduces the affinity of XIAP. XIAP is essentially the scaffolding protein that when it binds to RIPK2, it ubiquitinates RIPK2, and then produces the downstream cytokines that you see, such as TL1A, TNF, and IL-23, which themselves are all validated targets.

We have some materials in our corporate presentation that actually outline our molecule and how we approach this. Looking at this with respect to the XIAP binding affinity, what this ultimately means for RIPK2 scaffolding inhibition, whereby we were able to achieve 100% scaffolding inhibition, and then achieving the most robust inhibition of downstream inflammatory cytokines, which we think is ultimately what leads to the clinical activity that we saw in our phase II study.

Yeah. Of course. I think first it is important to note, this was the first time a RIPK2 scaffold inhibitor has been taken forward into ulcerative colitis.

Our first goal here was really to make sure that we had a safe molecule that was well-tolerated and learn as much as we could about the potential efficacy profile and confirm that this is a mechanism that we wanted to invest further capital behind. At the time that we started the study, we had 3-month toxicology results, and therefore, we were limited to only being able to dose for 12 weeks with our molecule during this study. As an inducement for patient recruitment, we also offered vedolizumab as a maintenance treatment, essentially because this is critically important for both investigator and patient interest in any kind of modern IBD trial. We took forward 2 doses, a 10 and a 20 milligram dose, and this dose selection was informed by an ex vivo TNF stimulation assay that we did in phase I.

What we did is we were going through the MAD cohorts. We would take the blood from the patients, and we would stimulate it with peptidoglycan, which is a component of all bacterial cell walls and is ultimately what activates RIPK2 after it binds to the NOD receptor.

Got it. What we observed is that at doses of 20 milligrams BID and higher, we were able to achieve maximal inhibition of RIPK2 signaling.

We define that as what you observe in a RIPK2 knockout cell, which is 90% inhibition. That was the high dose that we took forward. Going back to my initial point, we really wanted to understand if there was a potential for any kind of dose response and how maximally do you have to inhibit the target to have activity. We also use the 10-milligram BID dose, which achieves about 70% coverage of the IC90 during the dosing interval. That allowed us to test two doses. Ultimately, we expected both doses to be efficacious, and we saw activity with both of these doses in the trial.