Hello everyone, and welcome to the latest in the H.C. Wainwright Inflammatory Disease Mini-Conference series of fireside chats. My name is Ram Selvaraju. I'm a Managing Director and Senior Healthcare Equity Research Analyst here at H.C. Wainwright. I'm joined here today by members of the management team of Equillium. Equillium is traded on the NASDAQ under the ticker symbol EQ. We cover Equillium with a buy rating and $4 12-month price target. I'm joined here today by Bruce Steel, Co-Founder and Chief Executive Officer, and Stephen Connelly, Chief Scientific Officer and also Co-Founder of the company. Welcome, gentlemen. Thanks, Ram. Thank you, Ram. Pleasure to be here. So I thought perhaps we could start by discussing Equillium's acquisition of Bioniz, which brought in your current technology platform and several lead assets, and perhaps talk about how this platform can generate multi-cytokine inhibitors that are of manageable size with drug-like properties, as well as how quickly they can formulate new candidates and feed the pipeline of the company. And then we'll talk a little bit more about specific assets in this portfolio as we get further into the conversation. Great, Ram. Thanks for the questions. So I think maybe Steve and I can both sort of speak to this question. So we started Equillium really with a mission to develop highly impactful therapies for patients with high medical need in the broad field of autoimmune and inflammatory disorders. We started the company around our foundational asset, itolizumab, that we partnered with Ono Pharmaceutical, and we'd be happy to give an update on that as we get further into the discussion this morning. But the acquisition of Bioniz was, I'd say, the end result of a mission and goal we'd had for quite some time to broaden out our pipeline with novel, best-in-class, or first-in-class therapies. We felt that the underlying technology platform that we acquired along with the clinical candidates, including one that had already been through robust proof of concept in man with EQ101, was a very good fit with what we were seeking in terms of the ability to really have a dramatic impact on patient lives if these programs are successful in this overall approach of developing in a single therapeutic agent the ability to target multiple cytokines in a single agent. So this was core to our founding strategy, and we're very pleased at this point to have EQ101 coming up with our first dataset from the program in patients with alopecia areata. I'll turn it over to Steve to maybe expand on the programs and the underlying platform capability and how it gives us sort of a discovery engine, if you will, for additional drug candidates. Yep, thanks, Bruce. Maybe you can go down a few slides to the description of the platform here. Yeah, keep going down. Yeah, there we go. So this is a platform that essentially comprises of a mix of proprietary and non-proprietary approaches. Those that are sort of industry tried and tested, along with our own in-house proprietary techniques where we can identify these multi-cytokine activators or inhibitors. Now, we've all seen the industry sort of target the or look at the targeting of multiple pro-inflammatory cytokines, right? Go for more than one. Go for those that have some obvious overlapping synergy or redundant activity, but also trying to avoid the sort of challenges with targeting pathways that inhibit many cytokines because that's likely too many and they were hitting physiological targets. So here, this is a platform that allows us to target what we call shared upstream receptors. So these are receptors that are the home for multiple pro-inflammatory cytokines. A good example of this would be IL-4α, which is the home for both IL-4 and IL-13, and that's the target of Dupixent. So on these multi-cytokine receptors, we can inhibit multiple pro-inflammatory cytokines. We can drive the inhibition of synergistic or overlapping pathways to generate a more effective way of modulating biology. And in the respect of autoimmune inflammatory disease, we have pathways that we can target that are much more effective at inhibiting T-cell activity and T-cell cytotoxicity. Now, one of the benefits of this platform is that because we're based on naturally occurring molecules, either the entire protein if we want to agonize multiple pathways or fragments thereof if we want to inhibit them, that's already been shown to be effective in the field. This is really about building a better mousetrap and targeting the right targets. Now, these can be flexibly modified through pegylation, lipidation. We can add unnatural amino acids. We can derivatize these, or we can even fuse these to other monoclonals to give us improved drug profiles or tissue targeting properties. And along with that, we have broad IP covering the platform, methods of treatment, and composition of matter. That's allowed us really to generate a number of different multi-cytokine inhibitors and activators that we think drive a lot of value in a variety of different therapeutic settings. So, Steve, maybe you can just clarify for us how quickly you can generate new candidates using this technological approach. Are you able to have some advantages with respect to time to hits to leads or time to optimize lead? Yes. So we use a mix of sort of screening, sort of blind screening, and rational design. Now, really, where our advantage is that we're leveraging already well-characterized natural biology, right? So we're not looking necessarily for new targets. We're looking at hitting hard-to-hit targets or suboptimally hit targets, right? So we already have an enormous amount of data on the biological rationale, the therapeutic utility of those. And then we have a lot of crystal structures, screening data, and commercially available reagents to go after these. And so once we have these identified receptors, we can use that information to generate these fragments. Now, these fragments can be made either biosynthetically or synthetically, screened very rapidly, and then we can test that fusions to generate these sort of different therapeutic profiles, be it extending the PK or actually giving more bioavailability and GI restriction if we think about what we're doing with EQ302. So that's actually a very rapid process. So the screening process here, sort of a hit-to-lead, is somewhere between 6-12 months to generate an optimized molecule that could be then taken forward to your sort of IND-enabling group set. Great. So turning our attention now to EQ101, which is formally the most advanced candidate generated by this technology platform. Perhaps you could walk us through the rationale for blocking IL-2, IL-9, and IL-15 in this tri-specific manner and what implications that has therapeutically, as well as how this facilitates a broader inhibitory profile versus Janus kinase inhibitors or JAK inhibitors, such as ritlecitinib, otherwise known as Litfulo from Pfizer, and baricitinib, otherwise known as Olumiant, which was originated at Incyte. Yeah, sure. So the EQ101 targets the common gamma chain, and the common gamma chain is the home of six cytokines: IL-2, 4, 7, 9, 15, and 21. So six very important cytokines critical for the activation of TBNK cells. Now, what's important here is the relationship between some of those cytokines. If we go to the next slide, Bruce, IL-2 and IL-15 are critically important to the activation and proliferation of CD4, CD8, and NK cells. Now, when you block IL-2, IL-15 can actually compensate. And by inhibiting both IL-2 and IL-15, you have a much more superior way of being able to inhibit those CD4, CD8, and NK cells. IL-9 is important for dermal inflammation, and it's become more sort of widely characterized in a number of different indications where, for instance, Emma Guttman's work in both atopic dermatitis and alopecia areata highlights IL-9 as a very important type 2 cytokine for dermal inflammation. So this trifecta of cytokines goes after namely the CD8 and NK cells that are driving cytotoxic activity and destroying the hair follicle and the type 2 responses that seem to appear to create this rumbling, latent inflammation in the skin that is as yet unresolved. Now, when we think about the JAK inhibitors, the JAK inhibitors are targeting, in some instances with the pan-JAK inhibitors, 50+ cytokines, right? If we think about baricitinib, tofacitinib, ruxolitinib, etc., they have an extremely broad range of activity. And many of those cytokines that they're suppressing are physiological. So there's obviously some clear downside of doing that from a safety, tolerability, and toxicity perspective, and that's been well characterized, and I need not elaborate further on that. Now, something like ritlecitinib, which is supposed to be more specific for, for instance, JAK3, and JAK3 as a Janus kinase is exclusive to the common gamma chain for which we're targeting. So ritlecitinib, in essence, would hit all six of those cytokines: IL-2, 4, 7, 9, 15, and 21. But you'd argue that you don't really need to suppress all of those cytokines. And that's been sort of shown in multiple studies where IL-2, IL-15 combinations of antibodies have been shown to be effective, and then also in the studies where they've been able to use other blockers of those cytokines. So our argument is that you don't need to inhibit, call it 15, 20, 50 cytokines to get all your bang for your buck. You really just want to be targeting those key cytokines that drive cellular activity. And so that's why we think going for just IL-2, IL-9, and IL-15 is an approach that benefits us by having that selectivity, which we think will manifest in better safety. And then also from a potency perspective, if we move down 2 slides, I'll highlight one of the challenges with JAK kinases. Next slide. So this slide here, a bit of a complex slide, but let me walk you through it. This is a slide showing the activation of the pathways. Now, when cytokines bind to their receptor, they trigger three main pathways, and that's shown in the bottom left-hand corner. That's the PI3K, JAK, STAT, ERK. Now, when IL-2 binds to its receptor, it lights all of these pathways up, and that's shown in the middle bar of that left-hand side Western blot. Now, when you add Ruxolitinib, a very potent pan-JAK inhibitor, as expected, it inhibits phosphorylation of STAT 1, 3, and 5, but ERK and PI3K can still signal. Now, contrasted to that on the right-hand side, you can see in a similar fashion in the middle, all of the pathways are lit up when you add IL-2. But when you abrogate the binding of IL-2 by adding a multi-cytokine inhibitor, you inhibit all the downstream signaling. So I like to think of it as an analogy is that there are three rivers extending from a dam, and when you hit it with a JAK kinase inhibitor, you're blocking one of those three rivers. What tends to happen is the rivers flow down the two orthogonal pathways. Our approach is a more efficient way of titrating in a damming of all three rivers at the same time, and we think that could lead to a sort of more predictable, more consistent, efficacious response with better commensurate safety in that. So in a nutshell, effectively, what we are looking at here is something that is both more specific as well as more broad with respect to the downstream pathways, thereby effectively providing a way to interfere with the standard, let's call them, evasion strategies that occur when you apply, for example, a JAK inhibitor. Would that be a fair statement? Exactly. Rather than hitting one of three pathways to 50 cytokines, we're hitting all three pathways to three cytokines. Great. Now, looking at the programs that you are advancing with EQ101 and the key indications within medical dermatology, maybe you can walk us through how those indications were selected and what you consider to be the largest target markets, the most promising markets for EQ101. And in particular, perhaps we can talk a little bit about how you decided to prioritize the development of this candidate in alopecia areata. Sure, Ram. I can maybe speak to this at a high level. So when we acquired the program, we inherited a set of data around EQ101 that included first-in-man development that added a significant cohort of patients with cutaneous T-cell lymphoma. We felt that that data was very compelling, showed good proof of concept of the drug in that patient setting, as well as a favorable safety and tolerability profile for the drug. And some of those patients were dosed out to 70 weeks. So there was quite a bit of human experience with EQ101 from prior clinical development. When we acquired the asset, there were two INDs open, one for a phase 2/3 program in CTCL that was ready to go, as well as a phase 2 study in alopecia areata. CTCL, we do believe there's a high unmet need in this indication. There are very few drugs approved. In the medical derm space for this patient population, particularly the earlier stage patients, there's really not a lot that's really appropriate for treatment approved today. So we do think there's an unmet need there. The study that was laid out, we felt it was going to take quite a bit of time to recruit. In the commercial setting, it's relatively small. This is an orphaned indication with about 24,000 patients in the United States alone. Conversely, the alopecia areata program, we felt we could recruit this study quite quickly, significantly larger, I'd say, commercial opportunity, certainly from a patient number standpoint, with about 250,000 patients in the U.S. suffering from moderate to severe alopecia areata. At the time, no drugs had been approved, and it looked like the JAK inhibitors were marching towards an approval. So we very much like the overall competitive commercial landscape with the expectation and now subsequently approvals of JAK inhibitors, not a lot else in the development pipelines with novel mechanisms that we think are highly attractive from a product profile standpoint. So we very much like this commercial setup where EQ101 could enter the market following commercial development and proof by JAK inhibitors but come in with something that could be a very nice replacement for those programs. So we like the commercial setup. We also like the timeline to get to a value inflection point. And we're very much on track with our original thesis of getting to this dataset this year. Our guidance is quite tight that we'll have this top-line data in the Q2. This is a signal-finding study in this indication, following which we would certainly look forward to accelerating development in AA, but also use that as a starting point to think about additional expansion opportunity into somewhat tangential areas such as Vitiligo, where you have even a significantly greater patient population with very high unmet need, with, again, today, the only approved product is a JAK inhibitor. So I'll see if Steve would like to elaborate on any topics, but that's sort of a high-level overview of sort of our strategy when we initiated this clinical development program. I think the hair follicle-targeting CD8 and NK cells in alopecia areata and similarly the melanocyte-targeting CD8 and NK cells in vitiligo, there's a lot of overlap in those diseases regardless of sort of the clinical phenotype. Now, what we consider wide open spaces compared to something like atopic dermatitis, which has an enormous population but a lot of other drugs. So I think it's a clearer path for clinical and commercial development here for alopecia areata and vitiligo. But I could see us also looking at T2-solved patients with atopic dermatitis, those that don't have necessarily a high T2 signature, where a molecule just more broadly targeting the CD4, CD8, and NK cells might gain traction. But of course, we've seen a lot of new molecules and new modalities move into atopic dermatitis. So that's a little more in the long-term plan. I think next steps here, should we show benefit in Alopecia areata, could be to extend out in Alopecia areata and then also initiate studies in Vitiligo. I think between those two indications, that's blockbuster potential in a molecule. Great. So as we look specifically at alopecia areata and the ongoing phase 2 study, which I understand is coming up on release of top-line data relatively soon, next quarter, maybe you can tell us a little bit more about what you are looking for in this phase 2 study in AA to support accelerating development of EQ101 and what the key efficacy readouts are and how they would inform the potential clinical activity of this candidate. And if you are, in fact, expecting a therapeutic activity profile that might be more pronounced in a specific subpopulation, namely perhaps those with moderate severity of disease as opposed to those with mild or severe severity of disease? Thanks, Ram. A lot to unpack there. We do like to reference datasets that we feel are comparative and useful in that regard. In our corporate deck, we reference the baricitinib data that we think is quite useful as sort of benchmarks and keeping in mind that we are testing EQ101 at a single dose level over a 24-week period, and this is an open-label study. So maybe starting with this overall study design, we chose to conduct an open-label study, as have others and some of our peers such as Horizon, primarily for the reason that background placebo response rates across multiple studies with drugs that have now been approved for this indication demonstrate that placebo response rates are quite low, typically around 5%, ± a few points. So there's not a very strong placebo signal. Therefore, you can infer in a relatively small study, you can pick up signs of activity, is our belief with this study. We think given the patient sample size that we have recruited as well as the patient population mix, as you referenced, between a nice blend of the most very severe patients, which represent over a third of our patients recruited in the study that have greater than 95% hair loss via SALT score, effectively AU/AT patients, and the remainder more in that moderate to severe category, we think we have a very good opportunity to tease out a signal at this single dose level. We don't believe this is necessarily an optimized dose, but certainly one that should be sufficient to assess the signal of activity in this disease setting. So we would say, let's just be conservative and take 10% as the high end of an otherwise placebo response rate in a study. Something north of that would give us a reason to believe that we're seeing drug activity both from an overall SALT score, not necessarily meaning that we need a clear certain SALT 20 necessarily, but we certainly would be assessing that, but also changes in patients who respond from baseline, sort of what does that trend look like? So we feel confident in this study design and that it gives us an excellent opportunity for this initial signal finding that will then lead us to accelerate development into a broader program that would be placebo-controlled and look for dose optimization in the next set of studies. So that's sort of a high level. I want to make sure I didn't leave out any of the questions you'd asked in that set of questions there. No, I think that definitely covers that pretty comprehensively. I think in one context, it might be worthwhile looking at the safety side of the equation as well because, as Steve mentioned earlier, JAK inhibitors are widely recognized to be relatively dirty drugs. There's a class black box warning. So maybe you could talk a little bit about some of the main safety issues associated with broad-based deployment of JAK inhibitors and why you would expect this not to be a problem with EQ101 and how much of an advantage that might confer in the commercial context. Well, certainly in the commercial and I'll let Steve kind of elaborate on the technical side of it. But on the commercial side, I think it's very clear now JAK inhibitors approved. They appear to be having significant uptake and success. So the highest unmet medical need based on independent research that's been conducted suggests that there's a need and a strong desire for drugs that have perhaps a similar efficacy profile, maybe not even necessarily needing to work as quickly as JAK inhibitors work. But certainly for a disease that's not life-threatening or you're expecting to dose patients chronically over a very extended period of time, you want a drug that's safe and well-tolerated. And clearly, JAK inhibitors broadly as a class with their black box warnings are suboptimal in that regard. So we do believe that there's potential here for our drug to work comparably well to JAK inhibitors. But certainly, we are hoping to see that this drug has a more favorable safety and tolerability profile. There's, I think, good evidence from the initial set of human experience with this drug that our predecessors completed, but also scientific rationale as well. So I'll let Steve elaborate on sort of our thoughts here. Yeah. Now, the class JAK kinase black box warning largely stems from the long-term data that you see, right? And there's no compelling argument that I've seen that the safety necessarily safety and selectivity associated with refining the targets of those JAKs necessarily is going to abrogate that. And the FDA is going to take the conservative viewpoint of until shown otherwise. Now, inherently hitting the JAK kinase pathways, I think, is never going to be truly selective. And even with ritlecitinib, which is a JAK3-specific molecule, so ostensibly should only go after all six of those gamma-C cytokines for which we're targeting three, also hits the TEC kinase family, which is also a big family of kinases. Now, some of the big issues we've seen with JAK inhibitors in the sort of trial setting is hematopoietic disturbances, GI issues, general tolerability, increased infection rates, etc. To date, we've not seen any of that in our CTCL patients. It's been generally safe, well-tolerated. And many of those patients dosed beyond 70 weeks. Now, in a patient population that's not had hair for many years, they have time on their side. And I think we've seen in almost every dermatology indication to date, dermatologists will pay a premium for safety. So at the end of this year, probably three JAK inhibitors approved and no clear differentiation behind why if you failed baricitinib, you would go on ritlecitinib or vice versa. I think the fourth drug to be approved of a novel mechanism, if it carries that safety, could be the first drug that clinicians reach to because they may say, "Try this drug. See how you get on. And if we need to hit you with something harder, we'll hit you with something harder." And I think that's been played out time and time again in different dermatologic indications. So despite us being a potentially sub-Q injectable, if the safety is there, I think this is a drug that, although it's not oral, could still be reached for first because clinicians are really just going to err on the side of safety. And what we've seen is that play out in, for instance, Dupixent, which is used in adolescent alopecia areata. That takes almost a year to work to really start showing any signs of activity. But that's okay because there's a halo of safety around the use of dupi in patients. And clinicians would rather put an adolescent patient on dupi than perhaps walk them into a JAK inhibitor. So I think we're really excited about this study because I think what we as an industry want to see is a novel mechanism work outside of the JAK inhibitors in alopecia areata. So as a signal-finding study, I think really just being able to show we have a mechanism that affects alopecia areata and thus warrants further development is quite exciting and quite valuable. Great. So just very quickly, as we look at potential pivotal development, I think one of the important things to remind our audience about is the fact that there is a very well-defined clinical development pathway in Alopecia areata. I think this has now been trodden by several companies successfully, particularly when we look at the JAK inhibitor space. To what extent do you think those clinical development programs in the pivotal context represent a template for EQ101? And would you pursue any different kinds of clinical design parameters, assuming as and when you get to the pivotal stage? Yeah, excellent question, Ram. Yeah, we would think that the prior clinical development experience from the approved programs presents a pretty straightforward roadmap to follow. We have not pressure-tested whether or not with those approvals, there are significant changes or better approaches to get to an approval. Certainly, there could be. You might also think about evaluating transitioning patients off of JAK inhibitors as a potential approach. But I think we would be pursuing generally a frontline treatment setting. And the agency certainly has a comfortable approach to that that is already well laid out. So I don't know, Steve, any other thoughts on potential pivotal study strategy and designs? No, you hit it all there, Bruce. So perhaps we could discuss the next asset and Equillium's pipeline that comes from the Bioniz technology platform, EQ302. First of all, I think it would be helpful to better understand the selection process for the lead target indication of this candidate and what you found particularly appealing about that potential opportunity. And also, if you could perhaps give us a sense of whether thematically you expect Equillium in the future to kind of equally pursue autoimmune and inflammatory skin diseases, which are in medical dermatology, as well as inflammatory bowel disease, or if you intend to prioritize one versus the other. Sure. As of right now, I don't think we're prioritizing one over the other. Obviously, we're excited about both of these programs and the therapeutic breadth potential. We do believe we've got expertise in both of these areas that we've developed at the company. So we're excited about sort of the medical derm applications as well as for 302 specifically, the GI indications where we think this drug could be certainly a first-in-class, but potentially a best-in-class therapeutic approach. I'll let Steve kind of take you through the scientific underpinnings and rationale here. But yeah, Steve, go ahead. Yeah. So IL-15 and IL-21 are critically important for a number of different indications. They show up in atopic dermatitis correlating with skin severity, rheumatoid arthritis, lupus, IBD, Crohn's colitis included there, EoE, and celiac disease. Now, inhibiting IL-15 and IL-21 at the same time is critically important because they actually have a lot of synergy together. So they have overlapping synergistic activity as well as their own individual activities. And so in something like celiac disease where it's been most widely characterized, where both IL-15 and IL-21 are highly expressed in those patients, it's what's considered a two-hit model of pathogenesis. And we've actually shown in ex vivo data from patients that you need to be hitting both IL-15 and IL-21 to drive maximal suppression of those cells. Now, we chose celiac disease as sort of a lead indication, but we're very open to targeting other indications there, right? Now we've transitioned from a subcutaneous molecule to an oral molecule. It's a little bit more compelling to think about this for something like IBD than previously with an injectable. Now, if you have a gut-selective, small molecule, dual antagonist of IL-15 and IL-21 that's delivered orally, I think that's very compelling for a number of different indications. So we talk about Celiac disease as a lead indication because that's where most of the data is. But this certainly doesn't mean that that is the only indication that we would go after. There's other indications we can see such as vitiligo where IL-15s have been taken into. There's atopic dermatitis. There is rheumatoid arthritis. And there are other GI diseases that we could consider. Now, if we go down maybe, Bruce, and go to the landscape here and think about celiac disease and why we're excited about that as an opportunity, keep going down to the table. [It] is celiac disease has ostensibly 750,000-1,000,000 patients who are unresolved inflammation in the gut despite being on a gluten-free diet. That's the patient population the FDA has ring-fenced as targetable. That's the population that Amgen have been looking at targeting, Immunic, and Calypso, etc. Now, we already know from the underlying immunopathogenesis that it's a two-hit model, and IL-15 and IL-21 are critically important to that disease. And the IL-15s have shown some, albeit somewhat inconsistent, and moderate efficacy from their early-stage trials does suggest, like the ex vivo translational data, that a dual-suppressant, a dual-targeted molecule would be better. So why we like EQ302 for something like celiac disease is, first of all, there's no approved therapies and that you'd be treating GI inflammation. And we have a molecule that's not only bispecific in nature that's a better fit, I think, for the underlying immunopathogenesis, but it's also oral versus the monoclonal antibodies that are monospecific, typically given as an IV infusion every three weeks. So we think that's a sort of less attractive target product profile. The other one is there's a small molecule that could be dosed to treat flares. In something like celiac disease where patients can flare and then resolve, flare and then resolve, this allows you a treatment modality unlike biologics where you can actually treat them differently and think about treating the flares versus going on a biologic and then having to remain on a biologic. I think there's just a lot of advantages of this oral approach and bispecific approach in celiac disease. But like I said, we could certainly think about this being targeted into other different indications such as IBD. Now it's in its oral form. Great. I think we're running a little short of time. So in the few minutes we have remaining, perhaps we could talk about some of the legacy of Equillium, which involved the development of a monoclonal antibody called itolizumab. And it's targeting towards, among other things, lupus nephritis as well as acute graft-versus-host disease. Now, my understanding is that you have effectively partnered this with Ono Pharmaceutical Company, which is a well-known Japanese drug maker, and that this is effectively an option-based strategic partnership and that there ought to be a meaningful decision point to be reached by Ono later this year whereby they could seek to opt in fully, which would effectively constitute a significant value inflection point for Equillium because this could result in the payment of an amount of cash that could significantly extend your operational runway. Perhaps you could talk us through the rationale behind this partnership, how it brings value to Equillium's shareholders, and what you expect your runway to be if Ono were to exercise its option and what the option exercise is primarily dependent upon. Sure. I'm happy to address those questions. So first, the strategy. As mentioned earlier on the call, we've had a strategy from the very beginning of the company to expand our pipeline, to have multiple programs in development that could be best-in-class agents in areas of high unmet medical need. We felt that itolizumab had significant potential across a range of therapeutic areas. And I'd say we started really focusing in on partnering efforts in 2021. We were getting quite concerned around the capital market environment and what we viewed was a likely tough road ahead in terms of being able to raise equity capital from the public markets. Unfortunately, I think we did get that right. Maybe the downturn was more severe than I think most of us even would have expected. So we ramped up our partnering efforts in 2021, which resulted in our partnership with Ono Pharmaceutical that we signed at the end of 2022. And you're right. This is a fairly straightforward option-style agreement whereby Ono has effectively been paying for all of the development of the program during this exercise period on top of the upfront consideration we received, which was around $38 million at the time of closing the transaction. We have a reasonably robust budget here of about $8 million per quarter that Ono has been funding as this program is currently in a pivotal phase 3 study in first-line acute GVHD. And we have just recently completed our proof of concept evaluation for the EQUALISE study in lupus nephritis. The milestones for their option in terms of their decision-making are these two data deliverables, the top-line data from the EQUALISE study and the interim data from the EQUATOR study. What's interesting about these two data events, first, is the EQUALISE study. We've completed this study. We presented almost the entirety of the top-line data at poster presentations back in November at ASN and ACR. Ono has access to all of our data. And we have given guidance that we expect to provide this top-line data set in a more formal manner to Ono quite soon. I think in the coming weeks is the terminology we used in our 10-K. So this data set we view as largely de-risked from the perspective of getting it to Ono. The interim data is also interesting in that this is a blinded look to the company and to Ono. Our data monitoring committee will be looking at unblinded data, will make a recommendation back to the company based on predefined stopping boundaries for both futility and efficacy. Our base expectation based on our experience with itolizumab to date is that we would expect the study will read out to continue to conclusion. That's sort of our base case. I think that's Ono's expectation. We've been given indications from Ono that that's sort of the main criteria is getting through the futility assessment for them to proceed with this acquisition of itolizumab. We did tighten up our guidance around all of the above, which is that we will have both of these data sets delivered to Ono no later than Q3. They have a three-month window following the second data deliverable to make their decision. We do fully expect that Ono will make their decision during the course of this year. We would receive the upfront payment, which is a yen-based payment of JPY 5 billion current value, which is around $33 million based on recent exchange rates. Importantly to note, we also have $101 million of US dollar-based milestone payments, a significant portion of which are tied to clinical study starts. If Ono does opt in, we would expect Ono to likely initiate additional studies to maximize the value of itolizumab going forward. I think it's reasonable to assume that if they opt in, we'll not only get the upfront, but we will get at least one, potentially both of the clinical milestones in the relatively near term following their exercise decision. That would add, obviously, quite a bit of additional cash to our balance sheet. The upfront alone is worth roughly $1 per share in cash value, significantly more than that in the milestone payments we're eligible to receive. Our current runway guidance is that the just under $41 million in cash that we finish the year with, with our current burn rate that's quite modest, so around $5 million-$6 million per quarter, our current guidance that we've tightened up is we have cash into the second half of 2025 that does not contemplate Ono exercising. With Ono opting in, we would have runway considerably beyond 2025, likely out at least another 18+ months at a minimum. We're looking forward to the results of the Ono decision. We have a very close working relationship with the Ono team cross-functionally. We're prepared for transition work assuming they opt in. Great. So I think we're out of time. We're probably going to have to leave it there. But I think your overview has clearly defined what Equillium is at this juncture, a company that is pursuing multiple high-value, unmet need indications across the inflammatory and autoimmune disease spectrum with a very intriguing technology platform, lead assets that are poised to deliver value inflection points over the course of 2024, as well as a potential path to long-term financing of the company in a non-dilutive manner through your relationship with Ono. Thank you very, very much for walking us through all of those aspects of the company. And thank you to our audience for their attention. Rob, thank you for your time today. Much appreciated. Thank you.