Well, let's get started. Good afternoon, everyone, and my name is Arthur He, a Senior Biotech Analyst at H.C. Wainwright. Thanks for joining us today. We have a conversation with Dr. Kristin Yarema, CEO of ImageneBio. Kristin, thanks for coming down. Thank you so much, Arthur. It's great to be here. So, Kristin, for people meeting ImageneBio for the first time, could you give us a quick overview about the company and what is the leading asset, and what are you guys trying to do with that? Absolutely. ImageneBio, we're headquartered out of San Diego, and our lead program is Olevaprubart. It used to be known as IMG-007, but now we have an INN name, so it's Oleva. This is our next-generation receptor-directed monoclonal antibody targeting OX40. We believe it is truly next generation and highly differentiated. I'm sure we're going to talk about that. That's what we're doing, and we're pursuing Oleva in both moderate to severe atopic dermatitis, as well as alopecia areata. Sure. Thanks, Kristin Yarema. So I guess for OX40, since the beginning of the year, it's been quite a journey. Two of the program has exited in the atopic program. I guess a lot of people reasonable question if the OX40 is still a validated target. I guess your answer is no. Why is that a wrong read? Yeah. So look, I'll be the first to say that the OX40 space has played out rather more dramatically than I think anyone anticipated. Our thesis from the beginning, before anything happened, was that the first two programs in the space, rocatinlimab and amlitelimab, were very unlikely to uncork the full efficacy potential of this pathway and of OX40 blockade. There are different reasons for that on each side. The whole reason that I joined ImageneBio and came in to help drive this program to become a medicine for patients and create value is because we thought there was a tremendous opportunity for a differentiated molecule with the right features and attributes to show a lot more efficacy than either Roka or Amli with a favorable safety profile. We engineered in those features into this molecule from the beginning. Now we're studying them in phase IIb, which is our adaptive study, which is ongoing. Sure. You speak of the differentiator of the Olevaprubart. Could you elaborate that and also give us more color why those kind of special features of Olevaprubart is important in the clinical? Yes, absolutely. I said we're headquartered in San Diego. We're technically headquartered in a suburb of San Diego called Del Mar. Del Mar is famous because it has a big horse racing racetrack. I like to think of the features that are in our antibody as a kind of trifecta of important attributes. There are really three things that we hone in on that we think are critically important. The first is that the antibody is raised against the receptor, not the target. Rocatinlimab was also against the receptor, but it was a depleting antibody. Ours is not, and we're going to talk a whole lot about that in just a second. We always thought that targeting the receptor would be the approach that would be more amenable to maximum efficacy. Through OX40 blockade. Because the receptor is expressed on activated T cells. If you want to get complete coverage of your target as quickly as possible and maintain that coverage, we think targeting the receptor is the way to go. The other molecule, amlitelimab, that targeted the ligand, and I think we saw in the data that it was less efficacious overall than rocatinlimab. We feel we can go even to a much higher level. I see. But we were encouraged by the evidence in the field. The second feature is that, as I said, our antibody is non-T cell depleting. So it carries a mutation that silences the ADCC function. In contrast, the discontinued rocatinlimab had an enhanced, it was engineered for enhanced ADCC activity, and they published in The Lancet, very clear depletion, deep depletion of the T cell population. So it didn't just block the signaling, it killed the T cells. In contrast, what we do is just attenuate the signal but maintain the T cell population and the other important functions of T cells. So that's important for two reasons. It's important for efficacy, because rocatinlimab showed a lot of side effects. I think we're going to talk about Kaposi sarcoma. But they also saw quite high rates of treatment emergent fever, pyrexia, chills, aphthous ulcers, headache, a constellation of adverse events that has been associated with ADCC and T cell depletion. We haven't seen any of those. We've been doing ongoing blinded safety reviews across our entire program, and we've reported publicly that we have seen zero rates of any of those things. So we think one reason that you never saw much efficacy with rocatinlimab is they probably could not give a sufficient exposure. You couldn't really dose range that molecule because of the acute adverse events. But T cell preservation is also important from a safety point of view. So we should be able to appropriately dose range Olevaprubart for more efficacy, but we're not depleting the T cells, and so maintaining their function. And then the third feature that has been engineered into Olevaprubart that's very attractive is it has a long half-life. It's about 35 days. So we think that that opens up the opportunity for very patient-friendly dosing intervals. In our ongoing phase IIb study, we're looking at monthly as well as quarterly dosing, and that's just the starting point. It may be possible over time for us to go to even wider dosing intervals. I see. I guess, you mentioned about the Kaposi sarcoma. Obviously, that's the kind of elephant in the room. But I want to see what you're thinking about the real issue for that risk for the OX40 access and the reason or how you guys can mitigate those risk for Olevaprubart. Yeah. No, I appreciate the question, Arthur. For anybody who's following this that may have missed the memo, across the two programs that were ahead of us and were discontinued in atopic derm, there were four confirmed cases of Kaposi sarcoma out of about a number of thousands, maybe 7,000, 8,000 total patients across the programs. The cases all seem to have been in a particular sort of clinical phenotype. So elderly men, potentially men with a history of sexual relations with other men, and it has also been circulating out in the community that those cases of KS went away upon removal of the study drug. What has been seen in these programs ahead of us is definitely a signal worthy of attention and to take note of. We don't know if this will be something that we have to deal with with our program or not. We have not seen any cases of Kaposi sarcoma, nor even anything suspicious or remotely resembling that. And we do think that our molecule could have the potential to be safer not only than rocatinlimab, as I mentioned, but also, it has the potential for favorability toward amlitelimab, again, because of that receptor targeting. The ligand that amlitelimab targets is expressed on cells that are the known reservoir of HHV-8, the virus that causes Kaposi sarcoma. We like our molecule. We do want to keep an eye on this issue, and I think we're very favorably positioned to do so, Arthur, because when you know the type of clinical phenotype that these cases have emerged in, and again, the view is that it's been a quite consistent clinical phenotype, you can take measures to really ensure that appropriate patients are enrolled in the study and that appropriate physician-patient dialogue can take place. And we've incorporated some of that into our study. So we've looked very carefully at inclusion and exclusion criteria. We have done a lot of training, which our investigators have really appreciated on the whole topic of KS, and we have really instructed and counseled people how to properly monitor, observe, and have appropriate conversations between patients and physicians. We also remain very interested in the prospect for assaying for HHV-8. If you're not very familiar with HHV-8, this is one of the family of human herpes viruses, latent herpes viruses, and it's not very prevalent overall in Western populations. We think it's only somewhere a few percent, somewhere between 3% and 5% overall in Western markets. And that prevalence is inclusive of a much higher prevalence in certain subpopulations, such as MSM or elderly men of Mediterranean descent. So if one had an assay, one could potentially screen for patients to see whether they even were positive for HHV-8 at all. If you don't have HHV-8, you are certainly not going to get Kaposi sarcoma. So I think we see, as the dust has settled on this topic somewhat, that the view in the community is it certainly is something to watch, we're very vigilant in our program, but that overall it should be manageable. The real place to keep the eye on the ball is around the amount of efficacy that Olevaprubart might deliver. So when we think about how can value be created, what is the profile of a drug that can be commercially successful? You really have to have definitive efficacy, you have to have market segments that you can target, and you have to have safety that rides along with that. So let's just put the efficacy need into a little bit more perspective. Atopic dermatitis is a very heterogeneous disease. Yeah. Today, we basically have 50 million moderate to severe AD patients worldwide. Only about one in eight maximum, somewhere between one in 10 and one in eight of those patients, will ever even receive a biologic therapy. Of those, 30%-40% are not going to get the kind of response that they want from that therapy. At the same time, we really have, in the U.S. at least, only three real classes of approved advanced therapies. We've got dupilumab and the IL-13s, kind of IL-4, IL-13 class. We have nemolizumab. It works on IL-31. Doesn't really address disease symptoms- Yeah -other than itch. Then we have JAK inhibitors that work, but carry their own significant safety liabilities. So we really need different mechanisms that can add to what we have with the potential to treat atopic dermatitis effectively, and I want to emphasize effectively, in a different way. In particular, mechanisms that can treat disease more broadly than just focusing on TH2-driven disease, which is where- Yeah -dupilumab, IL-13, emerging STAT6 inhibitors would all fit. Our thesis, and what we are looking for with this phase IIb dose ranging study, is to show that with Olevaprubart, we finally have the right molecule targeting this pathway with the right cluster of features. And by appropriately giving enough exposure and having the right molecule to begin with, we can see levels of efficacy that frankly were never seen with either rocatinlimab or amlitelimab. Thanks, Kristin. That is a lot of very useful information there. I guess you touched a little bit on the adaptive trial. I guess you guys guided for the readout at the fourth quarter next year, so maybe you can set up some expectation for what we should expect for that readout. Yeah, absolutely. That is our guidance. The study is ongoing. It has been up and running for a little over a year at this point. We have been very happy with our recruitment, and things are going well with the study. We are very intentional about the study. In fact, we amended it once to even further improve the design based upon some of the learnings that were coming out of the amlitelimab and rocatinlimab program, to really make sure that we were fully dose ranging it, and that we were going to come out of this study with absolute clarity on what would be the dose to carry forward into phase III. We are looking at two different doses, two different dosing intervals, and unlike previous programs in this space, we are also really working with and studying very closely a loading regimen. We have seen loading regimens be quite impactful with some other drugs for other medical dermatology conditions. We think with Olevaprubart, in addition to it just being a loading regimen to get a high concentration of drug to the skin early, that we may see faster and deeper responses that really outpace anything we have seen with this class. We are encouraged from our proof of concept study data, where we saw at 16 weeks, over half the patients, 54%, had a mean EASI drop of 87%. They maintained that. 54% reached EASI-75, and almost a third reached EASI-90, which is a difficult benchmark to reach. That was with only three doses at week zero, two, and four. In our adaptive study, of course, we are dosing continually. Our primary endpoint is at 24 weeks. The study itself is actually looking at treatment for 48 weeks, and this will really be the first study, I believe, where we will see the impact of continual dosing beyond 24 weeks. We certainly really have not seen that data from the programs that were ahead of us. I see. Let us shift a gear a little bit. I believe in the alopecia areata, Olevaprubart also kind of with just the three doses, they are keeping the hair growth until, I think, after week 36. That's right. Given that, I guess my question is, I know you guys are looking to initiate the phase II study in alopecia as well. What could be a phase II data you are going to call a good outcome for that study? Yeah. What you are referring to, Arthur, is that we have a second positive proof of concept study in alopecia areata. No one else has shown that kind of data with this mechanism, ever. But again, it was unoptimized. It was just three doses at week zero, two, four, and then following the patients out to 36 weeks. We saw a mean decrease of about SALT 30 for the patients that were enrolled in forward with phase II development in alopecia areata. We have guided that we will have some data for that in phase II in 2028. Good. For that study initiate, what's the gating factor now before the study gating? Well, there's no gating factor. We're capitalized through our Phase IIb readout in atopic dermatitis and to get the AA study going. We're thrilled we were able to do that on the back of a modest PIPE earlier this year. As you mentioned, our intention is that that study is up and going this year. Good. I think you mentioned you guys well capitalized, so what's the runway for the current cash in hand? Right. At our last earnings, we reported $136 million in cash. That carries us into Q1 of 2028. So it's inclusive of the top-line readout for the Phase IIb adaptive study. It doesn't carry us all the way through all of the data for alopecia areata, but it gets us with that study well in progress as well. I see. Last question is, you guys are going to have two poster at the upcoming EADV. So anything you want to remind us to pay attention at the conference? Yeah. So, one of the two posters really does. It's going to showcase the PK and why we've designed the adaptive study the way that we have. You'll see with real numbers, which you don't always get with PK data, how we're looking at a twofold range of Cmax, a fourfold range of total exposures. So, the adaptive study is meant to be really robust and definitive and has been carefully designed to do that. So again, others ahead of us have definitely had their problems with this pathway, but we don't think they had the right molecule, and I'm not sure they had the right study design either. So, take a look at that, and we will also be continuing to really invest in and build out underpinning science. So a scientific story and more of a research and translational medicine program to really elucidate a lot of OX40 biology that we think's been overlooked and not yet sufficiently developed. Awesome. Thanks, Kristin. Thanks for coming. Yeah. Thanks, Arthur.