Okay, great. Good morning, everyone. Welcome again to TD Cowen's 2025 I&I Summit. For this next session, very pleased to have Artiva join us. From Artiva, we have Fred Aslan, the CEO. Again, my name's Tyler Van Buren, Senior Biotech Analyst at TD Cowen. Fred, thank you very much for joining me. It's a pleasure. Thanks for having us, Tyler. Of course. For those of you in the audience, if you have questions, you can go ahead and submit them via the web portal, and I'll do my best to get them asked during our quick 20-plus minute fireside chat. I want to get to the very important update that you all had this morning, of course. Before that, maybe we could level set with an intro to AlloNK. Fred, if you could start by providing a brief overview of AlloNK and its mechanism of action, since it's somewhat unique from other cell therapies, that would be great. Sounds good. AlloNK is our allogeneic NK cell therapy product. We at Artiva, we focus all of our efforts on developing this one asset. Just to remind everyone, AlloNK is a non-genetically modified NK cell. Because we do not Engineer in a CAR, we use Monoclonal antibodies to do the targeting. Monoclonal binds, for example, Rtuximab binds to CD20 on the B cell. The Fc portion of the monoclonal binds to CD16 on the NK cell that activates the NK cell, and that is what kills the B cells, right? To date, we have dosed over 100 patients across oncology and autoimmune disease. Around 70 of them were in oncology. In oncology, we saw very high responses. We saw durable responses. That gave us the confidence that we would have a good chance of actually having interesting activity in the context of autoimmune disease. NK cells, why do they matter relative to T cells? There's one big advantage of using NK cells, which is, unlike autocar T cells or allocar T cells or T cell engagers, which are leveraging T cells to kill the B cells, and when they do that, you have the possibility of getting runaway CRS, you do not see that with NK cells, not just with our NK cells, but generally when you look broadly at all the trials that have been using NK cells. That confers a big advantage. Our regimen in totality is Cyclophosphamide and fludarabine as the conditioning regimen, plus the AlloNK, plus rituximab, for example, when you are using that to target CD20. This regimen was designed so that one can actually give it in an IV, an IV center in a community setting, right? We're talking about six visits to one of these centers. You get your IV infusion, and you go home. Part of the value proposition here for AlloNK is that this is designed to have cell therapy activity, but with a tolerability profile that looks a lot like an IV biologic. That's great. Thank you very much for that intro. One of the unique aspects of AlloNK is the manufacturing, right? Can you talk about how scalable it is, where you guys are at currently, where you can get to, and eventually what we should expect on the cogs side? Yeah, absolutely. Artiva is a spinoff of a Korean company called GC Cell. GC Cell developed this highly scalable process to scale NK cells starting 20 years ago. By the time Artiva was actually formed, that process was pretty much Nailed down. Since the beginning, we have been dosing patients as part of this highly scalable process. We source our NK cells from umbilical cord units. From one umbilical cord unit, we can make thousands of vials that have a billion Cryopreserved cells each. One umbilical cord unit, thousands of one billion cell vials. We vial our one billion cells in an infusion-ready media, and that has a shelf life of three to four years plus. It feels a lot like a biologic from the point of view of the shelf life, from the point of view of the scalability. When you're ready to use the product, it's thawed at the bedside, and it's a five to 15-minute infusion. We use doses of either a billion cells or four billion cells per dose for a total of three doses over a three-week period, right? Our projection is that those billion cell vials can be manufactured for $1,000 or less. If you think about the totality of the cogs in a treatment, if it's a billion cells times three doses, we're talking about $3,000 in cogs. If it's four billion cells times three doses, we're talking about $12,000 in cogs. That is very unique in the cell therapy space. We have the opportunity to price this product wherever we want and still have the potential for very high gross margins. How readily available are umbilical cord units? There are tens of thousands, if not hundreds of thousands of them available across dozens in dozens of blood banks in the country. Got it. Okay. So, plenty of capacity. And again, before we get to this morning's update, maybe you could just provide a high-level overview of the current AlloNK development program and ongoing studies. Yeah. We are right now exclusively focused in autoimmune disease. We leverage our oncology trials as a clinical experimentation that the therapy is very active, and that the tolerability has actually been strong. All of our development efforts are focused on autoimmune disease. We have specifically three trials in autoimmune disease. We have one investigator-initiated trial, and we have two company-sponsored trials. Across these three trials, we're investigating the following indications: rheumatoid arthritis, Sjogren's, Myositis, Scleroderma, Lupus, as well as lupus nephritis, right? From all of those indications, we announced recently that we are prioritizing rheumatoid arthritis as our lead indication. We can go into the reasons why we prioritized it, but we recently received Fast-Track Designation, and we stated that this is going to be the first indication where we will be sharing clinical response data in the first half of next year. Great. We'll get to that after we discuss this morning's update. Since you mentioned it, maybe you could just elaborate on why you chose RA as the initial indication. Was it based upon, you know, patients' kind of how enrollment was going or patient size or the opportunity, you know, the unmet need in these refractory patients? Curious to get your additional thoughts there. Yeah, look, it's really all of the above. I feel that, most of the companies in this deep B cell depleting space, and there are many of us, right? Our secret to success is going to be how we break away from the pack, how we are choosing indications where we are playing to our product's strength. Everything that you mentioned sort of plays to that decision. First of all, Rheumatoid arthritis has the largest population of patients that are refractory to standard of care, right? Number two, when we think about the fact that the potency of our therapy appears to be quite robust, as, you know, we showed today in terms of B cell depletion, and given the tolerability profile, Rheumatoid arthritis is one of those indications that if you want to have that kind of access and be impactful, you need to be administered in a community setting. So far, we think that, you know, our therapy has demonstrated the potential to have a strong degree of activity and tolerability in a community setting. Another aspect is the fact that, you know, we are utilizing a monoclonal for targeting purposes. Easier to choose an indication where that monoclonal has already been approved in that indication. That way, there is less regulatory friction that you're encountering. As you mentioned, enrollment is another element that one takes into consideration. Given the prevalence of Rheumatoid arthritis, that also points to a favorable place. For all of those reasons above, it made a lot of sense for us to pursue RA as our lead indication. Okay. Very helpful. Makes a lot of sense. Now getting to this morning's update, maybe we could start with the safety and translational data, and but specifically safety that was presented. Maybe you could provide a brief overview of the safety that was presented, why you're not seeing CRS, ICANS, like other cell therapies, and why infection rates are low and you're seeing virtually no hospitalizations. Maybe you could just provide a few thoughts there. Yeah, absolutely. Look, I can share this from the point of view of my journey with it. We never expected to see CRS in our patients only because of the experience that NK cells in general, but the experiences that we had in oncology. Same with ICANS, right? With regards to infections, the one question that still remains quite controversial is this notion of how acceptable is the lymphodepletion, right? And what are the consequences of actually lymphodepleting patients? What the results we showed today, I think, debunks some of this myth that lymphodepletion is not acceptable as part of a treatment regimen. I think what we were able to demonstrate is that whereas lymphodepletion does cause all patients to have a period of a few weeks when they are neutropenic and lymphopenic, if you are providing anti-infective coverage to most of these patients, you are able to navigate that window when patients are lymphodepleted. What you're left with are the side effects of rituximab, you know, which stays in the system for several weeks. What's special about this is once you are done with this window, when you are under the effects of the lymphodepletion and the rituximab, you're giving these patients an opportunity to be drug-free, right? I think that the highlights of the safety data is that whereas we know that any of these deep B cell depleting agents have side effects that need to be monitored closely, right? People have been, even though many companies talk about the idea of taking these therapies to the community setting eventually, we were able to actually start there because of that differentiated safety profile. We are showing that managing our therapy is a lot closer to managing an IV biologic than it is to what you typically think of when you think of cell therapy being administered to a patient. That's great. Clearly, in all combinations, the cell therapy or the antibody or something is contributing to safety to some extent based upon what we saw this morning. And you've been consistent, not to skew from a traditional lymphodepletion regimen or what, similar to what Shet used. But, you know, obviously there's a lot of people out there talking about reducing lymphodepletion. Are you thinking about reducing that, trying to reduce it or remove it, or do you not feel the need to do that given the safety that you've shown so far? You know, look, time will tell whether the people that are making it their top priority to eliminate lymphodepletion are actually focusing on the long pole in the tent. Because in our mind, the lymphodepletion was never, such an impediment the way that many of the people that do not use lymphodepletion make it out to be. I think that as a field, we're all trying to prioritize efficacy. Autocar T has established a very high bar of what the efficacy is. As a drug developer, you know, should I be focused on trying right now to optimize the tolerability of it, or should I be trying to push that efficacy as high as I can while maintaining a tolerability profile? What I would say is I am very pleased with our decision to embrace lymphodepletion to drive as high of an efficacy as we can given the safety profile of lymphodepletion. I think today we have proven that it can actually be quite tolerable. I think in time down the road, one can think about opportunities to actually remove the lymphodepletion. What I will tell you is that other than a few case reports of two, three patients by different companies, there is no evidence that cell therapy without lymphodepletion actually works or that it actually works anywhere near what autocar can do. For now, we're pleased with our decision, and time will tell whether all of these efforts placed on eliminating lymphodepletion are actually worth it at this point until people establish really good efficacy for those patients. That's great. Since you started talking about efficacy, maybe we'll get right into it. So with the B cell data presented this morning, what gives you confidence, one, that you're seeing sufficient B cell reductions for meaningful and durable clinical responses, and then two, that the B cell depletions you're seeing are different from what would otherwise be observed with a CD20 monoclonal antibody alone? Right. The mechanism that we are all working on is a deep B cell depletion that actually eliminates B cells in the tissues, right? What we are trying to de-risk one step at a time is, first step is you want to make sure that even when using a TBNK assay, you're not seeing B cells present after you treat. Not everyone, even using a TBNK assay, has showed consistent B cell depletion. I believe one needs to, at a minimum, show that. B cell depletion is necessary, but not sufficient to know whether the drug is going to work or not. The next layer that I would suggest is utilizing a high sensitivity assay like what we showed today. There, using a, you know, 50 times more sensitive assay, we're able to show that, again, we eliminated all the B cells that could be detected. Again, I think that that is necessary, but still not sufficient to know whether it's going to work or not. We know that if you have samples from tissue, that is another insight that one can have, though those are hard to get and they're only going to be in specific tissues for specific patients. Ultimately, what we need to see are the clinical responses. What we are trying to do is to do things on a stepwise fashion. I think what we have shown today is to show that so far we are trending exactly where we want to trend in terms of following the mechanism of action. In time, as we show clinical responses, we will get the final answer, which is, are you seeing the actual responses that matter in patients? Perfect. Now, with respect to responses that matter in patients, first half of next year, we're going to see first, clinical efficacy and response rate data. Maybe you should walk us through and investors through what we should expect to see with that release, how many patients will be included, etc. Right. So, look, what we believe and what we have seen from the autocar CAR-T data, and now it's great because as a field, we have data from, you know, probably 200 patients or more with autocar CAR-T. There is a clear trend that when you use autocar CAR-T, there are some clear benefits that come. But what we have also learned is that outside of academic centers, you are seeing a certain variability with degrees to patients. Everybody is responding, but the degree to which they respond can be a bit variable, which is the issue of actually sharing data on only two, three patients, like many companies have done. What we have guided is that we're going to be sharing data on at least 15 RA patients, with many of them having at least six months of follow-up, because we feel that's a large enough data set with at least some enough follow-up for us to have a sense of how many of these patients actually respond and what kind of durability do they have. The plan is to share that data in the first half of 2026. Great. Is six months of durability enough, or do you view that as kind of the lower bound of what you would like to see? Ultimately, what level of durability of ACR 50 response or ACR response in general would you like to see in these patients? You know, the six-month mark, I think, is useful as a milestone as part of this journey that we're all on, because what we have seen, particularly with TCEs and some of the ones that have been studied, is that whereas one sees an effect after three months, by six months, a lot of those effects don't necessarily sustain. That has been the case with some of the Academic work that has been done at Erlangen. And we have learned that when one uses BCMA, that gives the TCEs an opportunity to have longer durability, though that comes at a cost of the need for IVIG and vaccinations, etc. Six months is also one of those necessary, but not sufficient. I would argue that our goal is to see durability in the 12-24 month range, because then when you think about it, that means that you're giving a patient a therapy, you're monitoring for the neutropenia and lymphopenia, which is really a lab value during the first few weeks. You cover this patient with prophylactic Anti-infectives, and then this patient now is off of the chronic drugs that they're used to being on, which actually makes them immunocompromised. There is a chance that after you come out of this treatment regimen period, during that durability, you have a chance of having less infections than a similar patient on one of these other immunomodulatory drugs that are chronically given. We think that a 12-24 month window would be a really nice period of response for these patients that are already refractory to the standard of care. That's helpful. Can you just elaborate on the RA patients enrolled to date, what level of pretreatment they have received? Ultimately, as you think about, like, ACR 50 response, you know, what does standard of care do, and then what do you think would be meaningful to show in the initial data set? Yeah. So, there are a dozen products approved in RA. Most of these studies are usually run in either patients that are naive to any biologic or targeted therapy. So, think about somebody who has failed methotrexate, but they have never tried a TNF, or they have never tried a JAK. In these patients, it's possible with a biologic or a JAK to actually drive these patients to close to an ACR 50 response in around 50% of those patients. But as patients start to fail their first targeted therapy and then their second targeted therapy, their opportunity to reach an ACR 50 actually becomes a lot lower. So, what we are suggesting is that there's a big unmet need in patients who have failed at least two targeted therapies to actually have a really meaningful response. If we could come in with our therapy and actually give these patients an opportunity to have an ACR 50 response in 50% of those patients, then we're almost giving these patients an opportunity to have the types of responses that are only possible today when you're actually naive to all of these targeted therapies. That's the bar that we are trying to set for ourselves, which we think could really move the needle in the context of RA. We would be the first company to actually start a pivotal trial in RA in the deep B cell depleting space, assuming our conversations with FDA go well. That would be an appropriate bar and, in a way, living up to the potential of these deep B cell depleting therapies. Okay, that's clear. Any initial insight into what a pivotal trial in refractory RA might look like? We are planning to get feedback from FDA in the first half of next year. So, we're not sharing at this point too many details of what we're going to be proposing to FDA. But, you know, I just want to leave you with the following, which is things become a lot easier from the type of trial and the size of the trial that you have to run if your expectation of the treatment effect is actually higher. The reason why many of these autoimmune diseases have had very large registrational trials is because the treatment effect has actually been quite modest compared to whatever control you're using. But if you're actually expecting a significant difference from whatever that benchmark is, that gives you a lot more flexibility and efficiency in terms of how to do that. We know that we have been valuing the FDA not making some companies run randomized trials, but I would posit to you that even if you have to run a randomized trial, if your expectation of what the treatment effect is compared to whatever your control is, is high, you can still do that pretty efficiently. So, you know, for now, we feel pretty confident going into our FDA discussions that the conversation will be productive. We'll learn a lot at that point. Nobody has had conversations with FDA about such a large indication like RA. But again, we are hoping that if the treatment effect that we are targeting is indeed what we hope for, that that could make those conversations easier than the alternative. That's great. RA is a very large indication, as you mentioned. I think everyone's well aware of that, even if you're looking at refractory RA. What other indications do you think are most interesting, in terms of potentially pursuing in the future? Yeah. So, I mentioned the indications that we are pursuing today, right, that we are testing AlloNK in. And I would argue that they fall into a range of which ones do you almost need to have a drug that is not only efficacious, but quite tolerable for the community setting, right? I would argue that within that range, you can think of one end of that spectrum as, for example, Myositis. With myositis, you already have a large concentration of those patients at tertiary care centers. Usually, when they have severe disease, they have it pretty bad. The idea of them being hospitalized in order to receive a treatment is not as daunting as when you think of, for example, patients with RA or patients with Sjogren's, for example. Sjogren's is another very large autoimmune indication where it is unlikely that you're going to be treating these severe Sjogren's patients or you'll be able to access them broadly with an approach like autocar CAR T, and more likely that a therapy like ours, where you can have potentially a good degree of efficacy with tolerability, could be well received, right? That is how we are thinking about it. We're trying to focus on the indications that are both Sizable and that play to the strength of our product. Okay, perfect. We are well over time, but just want to end with a final question. Just what do you believe is the most underappreciated aspect of the Artiva story by investors right now? I think investors see the space as exciting, but they are getting overwhelmed by the number of companies in this space. They're just saying this space is really crowded. What they need to focus on is on the breakaway for each of these companies. Whereas there are 20-30 companies today that are focused on deep B cell depletion and, across a variety of different modalities, and they're working across a variety of different indications, one needs to think about what is your lead indication. Do you have the potential to be first? Do you have a good target product profile for the unmet need in that indication? They should focus more on that for each company rather than trying to figure out which of these products is the best deep B cell Depleter, because that's not the right question. The right question is the question we ask of any biotech company. What are you going after? What's the unmet need? Is your efficacy good enough? Are you going to be first, you know, around an exciting mechanism? Fantastic. With that, we'll go and wrap. Fred, thank you very much for your time. And thanks to everyone for joining. I believe we've got a lunch break and starting back up at 12:30 with Protagonist. Thanks again, Fred. Thanks, Tyler. Bye-bye.