Conference Transcript - ODTX 2026-09-23

Alex, Analyst — Stifel

Great. Good morning again, everyone, and thanks for joining us for our next Fireside. I have Colin Todd here, Senior Vice President of Strategy and Business Development at Odyssey Therapeutics to walk us through the story. Maybe I'll kick it over to Colin to sort of give a quick overview of the company, and then we'll get into a Q&A. So, Colin, over to you.

Colin Todd, Other

Great. Well, thank you, Alex, and thank you to Stifel for having us on the Fireside today. Colin 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. And today we'll obviously discuss, you know, several of our pipeline programs and upcoming catalysts, but I think first it's good to touch on some of the organizing principles of how we put the company together. So first, all of our programs are homegrown. Everything that we're working on are things that we've started since 2021. Second is that we're using two validated modalities to advance our portfolio, small molecules of protein therapeutics. And then the third is ultimately our goal is to, for medicines that we advance, to be the first or second to the market.

Alex, Analyst — Stifel

Great. So maybe starting with your lead program, your RIPK2, can you walk through some of this genetic and mechanistic rationale in IBD, and then we'll walk through the data that you generated so far?

Colin Todd, Other

Yeah. So first, I think it's 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 downtrend in the cascade. So this is something that we've seen RIP-K2 ubiquitination, both in patients with ulcerative colitis as well as Crohn's disease. And so 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 ATG1601. Both of these ultimately increase the risk of patients developing inflammatory bowel disease. And so we think supports the concept using human genetics of going after this target.

Alex, Analyst — Stifel

Yeah. So I guess, as always the case with small molecule development, human genetics is the start in a lot of ways, but then designing a molecule that works, the whole other, you know, challenge, right? So for ODO1, you know, what are sort of the key elements of designing, you know, a proper RIP-K2 inhibitor? Why have others been unsuccessful?

Colin Todd, Other

Yeah, so 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 RIP-K2 were targeting the RIP-K2 kinase function. And 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. and what was actually important was the scaffolding function. So from the very start of when we worked on this program, we set out to create a RIPK2 scaffolding inhibitor. And what our molecule does is it binds to RIPK2 and holds RIPK2 in a conformation that reduces the affinity of ZAP. ZAP 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 T1A, TNF, and IL-23, which themselves are all validated targets. So we have some materials in our corporate presentation that actually outline our molecule and how we've approached this, you know, looking at this on with respect to the Z-out binding affinity, what this ultimately means for rib K2 scaffolding inhibition, whereby we were able to achieve, you know, 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 on our phase two study.

Alex, Analyst — Stifel

Yeah, so let's walk through the 2A. Can you talk a little about the monotherapy design dose selection here? And then I want to get into the data specifically.

Colin Todd, Other

Yeah, of course. So I think first it's important to note, you know, this was the first time a RIPK2 scaffold inhibitor has been, you know, taken forward into, you know, ulcerative colitis. And so, you know, 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, you know, potential efficacy profile and confirm that this is a mechanism that we wanted to invest further capital behind. So at the time that we started the study, we had three-month toxicology results. And so therefore, we were limited to only being able to dose for 12 weeks with our molecule during the study. As an inducement for patient recruitment, we also offered vitilizumab 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 two 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 one. So 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, you know, RIP-K2 after it binds to the non-receptor. And what we observed is that at doses of 20 milligrams BID and higher, we were able to achieve maximal inhibition of RIP-K2 signaling. And we define that as what do you observe in a RIP-K2 knockout cell, which is 90% inhibition. So that was the high dose that we took forward. And then going back to my initial point, 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. And so we also used a 10-milligram BID dose, which achieves about 70% coverage of the IC90 during the dosing interval. So 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.

Alex, Analyst — Stifel

Yeah. So an open-table study obviously comes with lots of caveats for interpretation, but when you look at the totality of your data, like what gives you the most confidence in the clear signal here?

Colin Todd, Other

Yeah, so I think there's two components. I think that there's a very well-laid-out approach to running a modern IBD trial. So, you know, first we worked with a company that's been in the space for decades, Alimentive. They've been involved in the development of nearly every single IBD therapeutic over the last 20 years. We use their site-level information, their investigator-level information, ultimately make sure that we're going to the right sites that are enrolling real IBD patients and understand how to run these trials. All of the patients that we enrolled required an MES score of two or three, required rectal bleeding. And importantly, we use centralized and blinded endoscopy reads. So this is critically important to make sure that you're not having any types of investigator biases. In addition, our team was involved in all the site and investigator selection. So those were the things that we did to ultimately design the trial to give us confidence. But now that we have the results actually in hand, I think the most important thing that we see is you see concordance across all the endpoints that we've discussed. You see a stepwise function as you move from the most rigorous definition of clinical remission through endoscopic improvement, symptomatic remission, and then finally clinical response. In the patients that we see having either clinical remission or clinical response, we see a nice decrease in fecal calprotectin, which is a validated biomarker of ulcerative colitis severity. And then we also see very nice activity in the AT experience patients. So with respect to, I think, the most definitive data set that came out of it when we share this data with investors or with key opinion leaders is the strength of the signal that we saw in the AT experience population, because the placebo rate in this group is commonly in the low single digits. And so our 25% rate there is something that people were quite excited about.

Alex, Analyst — Stifel

So then how would you put this activity data into context with sort of what we have out there today at UC?

Colin Todd, Other

So I think this is where the mechanism of the drug is very interesting, because this is the only innate targeted therapy that's actually been advanced in oral cervicalitis to date. And so what that does is it allows us to get above, you know, where all of the adaptive immune system is being activated. And so instead of targeting a single cytokine, we have the ability to depress multiple signals that are ultimately likely to be involved in any particular patient. And so, you know, when you look at what we observed here, we essentially saw equivalent activity between the AT naive and the AT experienced patient population. So I think this carves out an interesting opportunity for us both to be used with diagnosed patients, given the safety profile that we observed, as well as the oral profile of our molecule, but also something that can be used in the AT experience population where traditionally you see a 30% to 50% reduction in clinical activity in this group.

Alex, Analyst — Stifel

Yeah. Yeah. Yeah. Yeah. And I guess you're going to have more data at UEGW coming up in a month or so. So what should we expect to see there?

Colin Todd, Other

So I think you can imagine this is a common question we get from the investor base. You know, as I noted, we tested two different doses in the phase 2A. And based on the results that we observed, which we've shared to date, we saw similar activity with both of the doses. And so what we ultimately did is after we had this data in hand, we went and we backfilled at the 10 milligram dose group. So that way we can further understand any kind of dose response relationship. So at UEG, we'll have an additional seven patients at that lower dose, taking the total set there to 15, which can be compared more fully to the 41 patients that we had at the 20 milligram dose. In addition, we will also be sharing additional data cuts from that study, and then also a whole suite of biomarkers and other assessments that we've been doing over the last several I think, as you appreciate, it takes a lot of time to get all the samples in, assess all the samples and then ultimately assess that with regards to all the variables that can ultimately be evaluated. So that'll be on October 20th. Dr. Bruce Sands will be presenting that on behalf of the company.

Alex, Analyst — Stifel

Great. Yeah. And so obviously there's a lot more going on beyond the 2A. Can you talk through the 2B? And then also I want to talk about the combination study as well.

Colin Todd, Other

Yeah. So we really see combinations as the future of IBD treatment. And so what we intend to do coming out of this study is actually start two different trials in the second half of this year. One of them will be a phase two, a combination study. This will be a combo that we're doing with betalizumab versus betalizumab plus placebo. This will be an active only trial. And this will ultimately assess the potential benefit of being able to combine our agent with an adaptive immune therapy to break the therapeutic ceiling. Despite the fact that we have a half dozen different mechanisms that are approved, pretty much all patients are somewhere between a 15% and 25% absolute clinical remission rate. And if we really want to change the treatment paradigm of IBD, we see combinations as the best way to do that. So that trial will actually have a poster outlining the design of that trial at ACG. That'll be about around October 13th, I believe. So we'll lay out a lot of the additional information for that trial there. with respect to the phase 2b monotherapy advancement. We haven't released the final design of that trial, but we will do so in the future.

Alex, Analyst — Stifel

Yeah, I guess sort of, you know, back to the combo, definitely agree on combination and IBD generally. I guess, why VETO as the partner to start?

Colin Todd, Other

Yeah, so there's a lot of different reasons, so I'll try to impact them as linearly as I possibly can. So, you know, the first thing when you're trying to think about a combination partner, particularly with an investigational agent, is starting with what are agents that are currently approved. If the agent's not currently approved, you have to go back, do preclinical talks. So that takes out the opportunity for things like TL1A, which is something that you think would be interesting in the future. Second, you want to have something that's well-characterized, safe, and broadly used across the field. Betalizumab checks all those boxes. It's essentially a first or second line therapy in most Western societies. And then the third is, you know, something that we think has a, you know, good chance of success as far as the various mechanisms. And so, you know, RIPK2 is targeting the upstream innate response. And, you know, betalizumab in targeting T cell trafficking is really targeting the most downstream step of the adaptive response. And so mechanistically, that gave us a lot of confidence and interest in testing this. And we've actually been able to see a few combination studies using betalizumab, which I've read out over the last year. So, you know, one of them was a study by Takeda, the Exegem 4 study. And in that, they were able to combine betalizumab with tofacitinib, achieved over a 50% clinical remission rate. And this also tracks with what we've seen in other case series that have been published. So very good precedent for it. We think there's good mechanistic rationale for it. And it's also something that investigators are quite interested in for patients.

Alex, Analyst — Stifel

Maybe pivoting to OO2 and SLC 15A4, it's another innate immune biology target. super interesting. I guess, can you place SLC 1584 in sort of the context of how people are thinking about this space in rheumatology, in particular, with targets like TLR78 and IRF5?

Colin Todd, Other

Yeah. So I think it's really important to think about the totality of the pathway because we have a lot of benefit of significant validation that's occurred over the last five or 10 years. So at the very top of many autoimmune and inflammatory diseases, you have pathogenic signaling that's being driven by either RNA or DNA. And the RNA will signal through TLR7 and 8, and the DNA will signal through TLR9. Both of those ultimately converge on SLC15A4. SLC15A4 adapts with another protein called TASL, and then TASL is ultimately what activates IRF5. So what we get by intervening at the point that we are doing so with our SLC15A4 inhibitor is the point of convergence for both TLR7, 8, and 9 signaling, but also allowing us to only block IRF5 that, you know, ultimately, you know, you could have a potential to have a variable indication selection between an SLC15A4 inhibitor or an IRF5 blocker, but, you know, to selectively block the signaling that we want to in the diseases we're going after, we think SLC15A4 is a great way to do that. And, you know, going to the more downstream end of this after IRF5. Activation of IRF5 leads to production of interferon, which we obviously know works in several diseases with the approval of anafrolimab. And it can also control pathogenic B-cell activity. And that's actually some of the data that we have added into our presentation that we think is really compelling here, is instead of just thinking about this as blocking TLR7, 8, and 9, this actually gives us a potential to have a selective B-cell modulator in a pill.

Alex, Analyst — Stifel

Yeah, and I guess maybe could you sort of compare and contrast SLC-1584 to TLR78 upstream? You've seen proof of concept, obviously, from that biology. What's unique about hitting it at this node versus upstream?

Colin Todd, Other

Well, so we know that these diseases are driven by both RNA and DNA signaling. Let's take SLE, for example, and we now have the benefit of both seeing fematorin, the molecule that B-line is developing, having a positive top-line result in SLE. We've seen the Empataran results now, which has shown positive top-line data in phase two and is now in phase three. So, you know, we have validation from both of those, you know, TLR7-8 blockers. But if you look at patients who have, for example, SLE, there's also a significant component of the disease that is being driven by autoantibody production, which essentially has this feed-forward loop of inflammation. And, you know, one of those is our DNA-driven antibodies. And so what we show is that our molecule is actually able to reduce the production of that feed-forward mechanism, whereby if you only use a TLR7 and 8, we don't observe that phenomenon.

Alex, Analyst — Stifel

Yeah. And you're going to have some more data on this in November at ACR?

Colin Todd, Other

We will have a poster discussing this program further at ACR and laying out more of the reasons why we're very enthusiastic to take this approach forward and really teasing out some of the more of the B cell biology. because we think this is an incredibly compelling molecule, you know, kind of given where the B cell depleter space has been going over the last 12 months.

Alex, Analyst — Stifel

So then maybe for the molecule itself, sort of can you talk about some of the preclinical properties so far and sort of your path forward from here?

Colin Todd, Other

Yeah. So, I mean, the molecule is incredibly potent, you know, a single digit nanolar potency. We've essentially been able to phenocopy knockouts in vivo. So, you know, again, showing that we're able to achieve robust target inhibition to a degree that we think is ultimately going to be very meaningful, very high selectivity. And I think similar to the rest of the small molecule approaches we work on, we really try to have a pharma-grade molecule at the end of it. And so, projected once daily human dose, sub 20 milligrams. And it's actually very important when you take the step back and think about long-term commercial use. The most successful modulators of all time have all been relatively low-dose therapeutics. And that's because that reduces the xenobiotic burden over time and reduces the risk of developing any AEs and tolerability issues.

Alex, Analyst — Stifel

Yeah, yeah, yeah. Makes sense. And then your plans moving forward are for a basket study. I guess sort of what's the rationale there? What kind of indications are you thinking of moving forward?

Colin Todd, Other

Yeah, so we're really approaching this with a basket because we see the opportunity to develop this in multiple places. You can see many different indications are being pursued by B-cell depleters, you know, anafrolumab is an agent that's been approved. We now see that expanding into other indications and ultimately also following the lead of what we've been able to see with TLR7 and 8. So that's what's leading into the basket design. It's really, we see a number of opportunities. The only indication at this point that we have committed to in this study is cutaneous lupus. And this is really to, you know, ultimately get the initial proof of concept results for this with something where we know TLR7, 8 works as well, potentially tease out some differentiation opportunities, and then also use skin biopsies to help understand the mechanism of the molecule, because that is something that will be incredibly valuable as we move forward into later stage development and pursue indications where that might not be feasible.

Alex, Analyst — Stifel

What kind of, I guess, what's the level of data or the quantum of data you would need to expand beyond CLA, get confident in the molecule, and think about other indications?

Colin Todd, Other

Well, we're going to be doing the other indications at the exact same time. We're not going to be sequencing this or staging this in any way. So, you know, again, CLE is used there as, you know, one of the proof of concept indications, but, you know, we plan on having data, you know, from these around a similar time point, and then we'll ultimately decide on the path forward from there with all that information in hand. The one thing that we will be doing, though, that I think is important is in the phase one, you know, again, building off of the precedent of what we've seen with TLR7A blockers, all of these use an ex vivo stimulation assay in their phase one trial, and all of these ultimately correlated to later stage efficacy, whether, again, it be with the empataran molecule, the fematoran, or an e-sci molecule, which is also being advanced as well.

Alex, Analyst — Stifel

Yeah. So then maybe let's pivot to OO3. You're at a high level, I guess, why should we all be excited about Treg biology?

Colin Todd, Other

I mean, if you think about potential applications on inflammatory and autoimmune disease, there's really not many that a better Treg might not be able to treat. This is something that gets to, you know, the root of disease by being able to have, you know, T-regs that traffic to the site of disease, T-regs that have better immunosuppressive properties. You really have a potential to treat, you know, a pretty broad swath of indications. You know, the first kind of tier of development that's been ongoing is in dermatologic diseases. This has really been done by Nektar and others in the field. But, you know, we show some of this data in our prospectus, you know, using an EAE model, which is essentially a murine model of neurologic disease. You know, we're actually able to see Tregs trafficking to the brain. We're actually able to see efficacy in a therapeutic setting where we don't see that with IL-2, which was also used as a comparator in that study. So, you know, there's a lot of opportunity with this agent. And, you know, we think that TNFR2 really gives us the opportunity to build on this first layer of validation that we're ultimately seeing with IL-2 based approaches. by not just expanding TREG number, but improving their function and improving their immunosuppressive properties and the stability as well.

Alex, Analyst — Stifel

Yeah. How would you characterize kind of the key difference between TNFR2 agonism and sort of low-dose IL-2 or RESPEG?

Colin Todd, Other

So, I mean, we view IL-2 as really providing some of the initial proof of concept for being able to use TREGs. But, you know, it's important to note you're fundamentally activating a completely distinct program within these TREGs. So IL-2 is entirely focused on expanding Treg number, whereas TNFR2 does expand Treg number, and we can see some of this in the Tregs bio-perspectus that was recently published, as well as data that we've published. But in addition to that, given the fact that you have this novel program that you're activating, you do improve immunosuppressive function. We've shown that with various surface markers. We improve the ability to traffic to tissues, both by counting Treg number, but also homey markers such as CCR8. And you're also able to initiate a tissue repair program. So there's a factor called BATF, which is actually linked to the ability of Tregs to repair damaged tissue. And TNFR2 agonism increases BATF as well. So we really see this as an opportunity to build on what we've learned with IL-2, but potentially make this a much more broadly applicable mechanism.

Alex, Analyst — Stifel

Yeah. So you alluded to some of your EAE data that you generated preclinically. Is there, what's the status of OO3 at Odyssey and sort of where do you think about indication selection from here?

Colin Todd, Other

Yeah, so, you know, IND enabling studies are ongoing. We expect to complete those in the first quarter of next year. In the middle of next year, we also expect to see the first efficacy data from T-Rex Bio. So, you know, based on what we see from them, as well as what we see from our ongoing IND enabling studies, and then also IL-2 will decide on the best path forward for the molecule.

Alex, Analyst — Stifel

Great. So maybe in the last couple of minutes here, can you talk about your current cash runway and what the embedded assumptions are there?

Colin Todd, Other

Yeah. So, you know, everything I've talked to you about today with respect to the RIP K2, SLC 15A4, and TNFR2 program are included in our, you know, base runway assumptions. We have $433 million in cash as of June 30th of this year, and that capital will ultimately fund us into the second half of 2028. So, you know, that will allow us to achieve both of the readouts that I talked to you about for the RIP-K2 program with respect to the Phase 2b as well as the Phase 2a combination. And it will also allow us to complete the SLC-15A4 inhibitor Phase 1, which we intend to file the CTA on later this year. Well, Colin, thanks for joining us. Really appreciate it. Thanks a lot, Alex. Thanks for the time.