Let's go ahead and get started here. Thanks, everybody, for joining us here on day three of the Piper Sandler Annual Healthcare Conference. I'm Joe Catanzaro, one of the Piper Biotech analysts. It's my great honor to kick off this next session here with ImmunityBio. Joining us from the company is their CEO, Rich Adcock, and their CMO, Bobby Reddy. Appreciate you guys joining us and making some time. Wanna obviously jump into Q&A in a bit, but maybe, Rich, I could give you a couple of minutes. You could introduce the company, let everybody know what you've been up to and what we have to look forward to. Certainly, certainly. Well, first of all, thank you for having us, and appreciate the time and the meetings that we've had to date so far on those. As you said, I'm Rich Adcock. I'm the CEO for ImmunityBio. And, you know, there's a lot of work that's been happening at ImmunityBio. I always describe ImmunityBio as a company that's an N of one, and everybody in this audience will understand what that means. And that we really have a product that was, not a product, a company that was founded by Dr. Patrick Soon-Shiong with a premise of: How are we gonna bring combination therapies to tackle some of the most complicated cancers that are out there? We're happy and proud that we're up to, hopefully, the edge of being able to bring our first to approval here and many more in the upcoming futures, what our goal will be. Great. So, with that, maybe we could jump right into- Yeah that potential near-term approval. Maybe just starting with N-803 and non-muscle invasive bladder cancer. What can you say, I guess, at this point, around the sort of current state of the ongoing review with the FDA? Yeah. So, you know, a couple of things. First, we, as we were working through the last review cycle, we really felt like we were working our way towards the approval on all of those pieces. At every step along the way, you know, the meetings that we were having and, and stepping our way through that one, when we did receive the complete response letter, we took it very seriously, obviously. And I think one of the things that we really focused our energy and intention on was to say, "Let's take the very specific things," 'cause one of the... You hate to say benefits, but one of the benefits of a complete response letter is it takes the 100,000 opportunities that exist out there for you to focus in, and it says, "Here's the handful of things we really need you to spend your time and energy on. Tell us how to bring those about." And instead of taking an approach and philosophy of saying, "Let's hurry up and ask the FDA for another meeting" right after we got it, what we really did is said, "We think they were quite clear. Let's work through and begin the process of really trying to address the issues that they've raised up, and then meet with the agency once we have very specific plans to not get an approval on the philosophy or theory of it, but on the specifics of what we're doing to try to address those." And when we had our Type A meeting, it was very productive and very positive with the agency. And so they were able to tell us, "Yes, the actions you've taken are exactly the types of things that we're we're expecting from you." Obviously, they always say it'll be a review issue, but something so we're, we're happy with that. We were able to finish the work and then submit or resubmit the BLA for approval. Yeah. So, maybe you could elaborate on that just a little bit. Yeah. I was pleasantly surprised at how quickly you guys turned around- Yeah ... that CRL into a resubmission, especially around a CMC issue. Yeah. I think there are always expectations that those type of things take much longer than expected. Maybe you could just speak to what allowed you to address some of those CMC issues in a pretty quick timeline. Sure. And I can't go into the full details of those. What I can tell you is when we received those, it's something that we looked at, took very seriously. The teams... This was one of the—it's actually the only product we have that was done by an outside contract manufacturer, which is somewhat ironic through those. But we don't treat it as though it's an outside drug responsibility. We've always treated it, because it's our product and our drug. And so when the issues were brought forward on those, they weren't, "You need to go back and start over on your process." The process itself wasn't what was being in question. It was really tightening up some steps along the way and us working through those. What they were asking for was some more data and some more clarification, and in doing such, it allowed us to move actually, we felt, quite rapidly, so that we could bring this to a point that say, "We're confident enough to be able to meet with the agency to say, 'Do you believe this will meet what you're looking for?'" And then, upon having a very productive Type A meeting with them, to be able to finish the work, 'cause it's still a large package. You know, it's nearly 700,000 pages when you submit this, and you have to reindex everything and bring everything back together, and so it was a large package. For me, personally, I was happy, but I will tell you, I was very surprised at how fast the agency responded to it. And honestly, I credit that to the teams that put together the reviewer guides. The entirety of the package is what's essential, but the reviewer guide sections of those, and specifically the hyperlinking that we were able to do inside of those, really made it a very navigable package. And so we believe that it was really targeted specifically what the agency was looking for, and that's why literally within two days, they came back and said they've accepted it as a complete response to the resubmission, and now the review process begins. What can you say about how the FDA, again, sort of during the first go-around? Yeah ... how the FDA viewed the clinical data package? Bobby, I'll let you start. Yeah. I mean, I think the good news is that there was no additional comments from the FDA within the CRL, so I think they viewed it very favorably. Ultimately, what they said was, "Please provide an update on safety." So this is actually the third update they've seen because there was an interim update, which we provided, and there was no new safety signals. And they said, "You can also have an opportunity to provide an update on duration of efficacy." So they did state: We don't want additional patients. We don't need a new trial. We don't need additional data on additional patients that have been enrolled. Give us the original study, just provide an update on the duration, which we've provided. And the important part of that is that the duration now, the median duration is now not met. So, you know, previously it was 26.6 months in the publication, but now it's actually not met, and we have a whole series of patients that continue to be followed with ongoing duration of response. One thing I thought that was interesting is that I, I think last we spoke, Rich, it sounded like the FDA wanted an update on the nine BCG- We did naive patients Yeah - that you guys had enrolled quite a while ago. Maybe you could just sort of speak to that, and why the FDA was maybe interested in getting an update on those patients. Why don't you provide the update, and I'll give you my suspicion as to why? Sure. So those nine patients are from the original phase I trial. These are BCG-naive subjects, which is different than the FDA submission, which is BCG unresponsive. But in that setting, these subjects had received therapy way back in 2014, 2013, and so there's long-term opportunity for very long-term follow-up. And of those subjects, there are six who are available for recontact. The study ended as a phase I trial. There was a very short limited period of follow-ups. We followed them through two years, and they were all disease-free at that point. However, at this point in time, they were recontacted. Six were available. Two had passed away from natural causes, completely unrelated to bladder cancer. One was just lost to follow-up. Of the six, six out of six remain disease-free for an 8+ median, 8+ years of median follow-up, without evidence of recurrence, so that's pretty exciting. I think when you look at this, you know, often what the agency is tasked with doing is saying, "I want to approve a new drug that is significantly stronger than the prior," which is a little bit. This is a whole new era that's being potentially ushered in here on these, and specifically around immunotherapies, fusion proteins like this, and you're seeing a whole new area of what we hope will be recognized as memory-like structures that are being brought about. And so really, they see the strength of the duration, which is very strong, unlike, you know, people have not seen them many times prior, and they see it increasing, and that's why they said, "Well, go back," 'cause that trial was a two-year trial design. They asked us to go back and try to find those nine patients, of which we were able to track six of six and be able to bring forward and say, "Six of six are still in complete response 8+ years later." So I, I believe they're looking to saying, "That's our best indication of what the future potentially holds." We don't know yet, for the rest of this, we've not reached duration. Maybe last couple of questions on the- Yeah ... the review process. I guess, your, your expectations around potential AdCom, I guess, if there wasn't one the first time around, I'm thinking we shouldn't be... have any expectations to have one this time around. And then pre-approval inspections, at the manufacturing sites, I guess any visibility into that, whether they've occurred or whether they're planned, how that's all going? Yeah, so I'll start with the AdCom pieces. They've told us actually a couple of times already that an AdCom not needed for this, and I believe it's just because of the clarity and the strength of the clinical data. However, I'll say this: It's. We've always felt as a company, obviously, we understand the severity and the importance of doing an AdCom, but when you have a strong set of clinical data like this, we're like, we "If that's what was required, we would be happy to have that type of a scenario." But they've specifically told us no AdCom required, and we don't believe that there'll be one again for this one here. We're working with the agency right now. We've just resubmitted, and we're working with the agency on all of these. Obviously, it's their full ability to do re-inspections, and so we're just in the process of trying to work with them to calendar and do whatever it is that they ask in these early days. Maybe we could shift gears and touch a little bit on sort of the commercial opportunity. Yeah. Maybe a two-parter one. How should we think about this initial label and the opportunity behind that? And then, sort of two, sort of the work you're doing now behind the scenes, potentially preparing for a U.S. launch. Yeah. Let me start with the latter, and then I'll come back to the former. Helen Luu is our Chief Commercial Officer, very experienced in the urology space, and she's fully preparing for a U.S. commercial launch. And so we're working with all the pieces, with internal and external resources, to bring all of these together. Obviously, the start-stops always make it a little bit complicated, in those efforts, but she's doing a fantastic job on all of the different activities on those. And so we do believe this will be a product, and not just believe, that we will be prepared, once we get approved for this, to be able to go to market. But more importantly, we're prepared, at least as we sit here today, assuming the FDA approved us with what we brought forward, with supply as well. And so it's not one of those things where that we'll get approval, and then there's gonna be a long time for supply. We're sitting here today, and again, it presumes and, it requires us to have, you know, the agreement on the final product here with the FDA, but we believe that we'll be ready to move and move forward to have product in the field right away. And I think that's really important because sometimes what happens is people get an approval, and it's a long delay for a whole host of reasons through those. I think as you. So it is, it is something that we do anticipate bringing, bringing to market ourselves. And you and I have talked about this in the past. This is a market, and this is a specific market, and I'll take it on two points. It's really important to focus on the prevalence versus the incidence. Most cancers, it's really important you look at the incidence because of the complexity of those. This is a cancer that people are able to live with, at least for some period of time, and because of the severity of the outcome, being a cystectomy, where they lose their bladder, they're doing everything they can to prevent that. And so this being a bladder-sparing treatment for those, the physicians are holding out, patients are holding out for those. And so the size of the market is actually bigger than what people do, because often when people size the market, appropriately so, they say, "Tell me what the incidence is." But we really look at this and say, we believe, and I say that we, is what urologists are directly telling us, is that it's going to be, especially for the first several years, a prevalent base disease state. And so it gives you a very nice market size to be able to address and bring forward with. Maybe on this sort of topic in terms of pricing, I know you guys probably can't speak to specifics, but if you could sort of point to potential comps. And of course, I think about, you know, Keytruda has a label in the, in this space. There's also another recently approved drug, though I don't know if they've disclosed their pricing strategy. Just wondering how we should think about that. You know, I'm not here in a position today to be able to disclose pricing. Obviously, that would be premature. We do know what the most recent ones approved at, and it's obviously quite high on those, and we understand why. It's a lot of capital. It takes a lot of time and effort to be able to bring a product like this to market, and that is important for be able to be able to receive back on those pieces. So we know internally what we'll set the pricing at. We've done all of the pricing work. We've done the tests with the market. We've talked with all the payers, not all the payers, but we've talked with payers. We've done the work on those, and so we're ready, and part of our commercial operations, commercial strategy is to be able to have that. And so we're just trying to finalize the work with the agency now, so that when we do get that approval, we can go to market right away. The other question I had is around this BCG shortage, and the potential impact or non-impact of that on use of N-803, which is going to be used in combination with BCG. I've always been hearing that there's temporal dynamics around the shortage, there's geographical dynamics around the shortage. What insights do you guys have into that, and what are you hearing from physicians currently on sort of where that all stands? Bobby, you want to start? Yeah. I mean, I think that's it. It's definitely a real issue. It's not a fake issue, but it's an issue that can be managed. So what we've heard consistently from urologists for several years is that because they've been experiencing this for five, six, seven years now, they've learned to manage it themselves. They have created supply systems where these large urology group practices, these large organizations, can share between individual offices and schedule patients in a way that they can manage this problem. So they've told us it's really a contrived problem and that they would prioritize the use of BCG for these patients in combination with N-803. Because, again, as Rich pointed out, the alternative is to lose your bladder. And so, you know, I think it's an issue, but it's an issue that can be managed, has been managed historically, and the urologists have stated to us consistently that they don't perceive it as being an issue going forward. The thing I would maybe add to that is, and it was pointed out to us, we didn't actually notice this right away, on Merck, who's the provider of the, of BCG for the United States, on their website, they had previously listed the United States actually as a shortage area. They had Canada, the United States, and others as shortage areas. This year, they updated it to just be Canada, but not the United States. I don't know. I haven't reached out to them to find out what that is. I have asked urologists what they're seeing, and what they've said specifically is similar to what you noted, is that it's... at times it is, at times it's not, and in areas it is, and in areas it's not. And so it does feel like it's maybe working its way through those or that the system is just adapted to overcome it. Great. That's, that's really helpful. So I mentioned there's been a couple approvals in this space with, with pembrolizumab and Adstiladrin. I guess, how do you think about the overall competitive landscape and some of the important differentiating features of the N-803 BCG regimen? Yeah ... and even the clinical data set relative to what those competitors offer? Bobby, I'll let you start, then I'll finish. Yeah. I mean, I think that the key, as we pointed out earlier, the key is that we have a significantly longer duration of response, right? So not reached, as compared to, say, 9.7 months or 16.6 months. And that's, I think, critically important because if you're a patient with this disease, remember, this is BCG unresponsive, so you've already experienced one relapse, and the next step is to lose your bladder. And there's a risk that you could progress into invasive disease or more significant metastatic disease. So it's really important at that point in time to find something that can work effectively. So we have a higher response rate than these other competitors that you suggested, and a longer duration of response. Now, in terms of complexity, it's actually relatively given because these people have been receiving BCG previously. They're familiar with the schedule, the urologists are familiar with the schedule. It's very simple for them to do. There's no change in their pattern or practice. So I think for the urologists, it becomes very easy. And for the patients, lastly, the tox profile is quite benign. So as opposed to a systemic agent, for example, where there are significant risks of serious systemic toxicity, including life-threatening toxicity, there's none of that. So for those reasons, I think it's probably- The thing I would really emphasize, and Bobby talked about this, is when you look at this versus what's out there or what's being developed, and we try to be very aware of all of those. We're the only ones... and because BCG is the current standard of practice, so everybody is familiar with that one. One of the brilliant pieces that Dr. Soon-Shiong, Dr. Reddy, and the others have done is they've really completely modeled it exactly following that. And so down to the electronic medical record in the urologist office, it doesn't have to change. Everything follows the exact same, and you get the clinical results with this. And so we believe that it's going to be a really easy adoption pattern, which is quite unique. So one thing you guys, I think, have spoken about is sort of the opportunity to maybe find a partner around N-803, specifically in the intravesical form and this initial opportunity. I guess, where does that thinking stand? What could a potential partnership collaboration look like? Yeah. Something we're still very open with. The board, as a whole, has talked about this in great detail. You know, as we sit here today, as we look at this, we think the United States market is something that's very appropriate for us as a company, the size with the consolidation it's undertaking, and it really gives us the ability as a company to have that, our own financial wherewithal under our own control. That said, this is a very large global market opportunity, and there's a lot of interest in this product on a global basis. And so we continue to evaluate and work through those. I think when we look at this, that's something that will likely make sense for us, but we're still working through the details because we know the more mature we get it, the better it does, one, for patients, but also for shareholders on those. The sooner somebody exits out or partners out with those, is the return actually becomes diminished for the long run. The other question maybe I had was around next steps in clinical development for N-803 within NMIBC, but outside of this initial indication. So help us understand, how should we think about the papillary subset of NMIBC, BCG-unresponsive, and then maybe longer term, moving into BCG-naive population? Bobby? Well, so in the papillary, we have phase II data, 80 patients. It's in the paper suggesting a much higher response rate. Well, I shouldn't say response, but disease-free survival at 12 months than the competitors that are out there, including the recently approved nadofaragene, which did get Category 2 compendia listing from NCCN. So we'd expect similar, if not better, listing and perhaps some off-label use. Now, in terms of a regulatory pathway there, we have had discussions with the agency. We've had a draft protocol submitted. So we do have a pathway there to take with a randomized trial, which could also... We're looking at could that trial also be used to support a global indication in NMIBC papillary. Obviously, we have a first-line trial or BCG-naive trial that's ongoing, that's been enrolling for several years. Now that we can take some of the BCG utilization pressure off because much of that BCG was being funneled into the second-line trial, which again, it's a good problem to have, but we have a number of subjects that are continuing on trial, continuing for years and years and years, and continue to consume BCG, which again, is a good problem, but is also a problem. So, that will allow us to free up some of that supply and help further enrollment in that pathway. And then lastly, we're looking at opening some trials in metastatic disease as well, because there's good early data in combination with checkpoint inhibitors, systemic, as Rich mentioned, systemic therapy. So that's kind of the continuum of bladder cancer. In terms of the metastatic, is that you're referring to specifically bladder? Yeah. I know there's been some other sort of areas you guys are pursuing, so maybe that's a good segue to- Yeah ... whether there are other opportunities outside of bladder for N-803 that you guys are interested in. I would say if you look at it from a kind of a company focus, first and foremost, and I'm gonna start in urology, I think bladder and prostate are very key opportunities for us. And if you step outside of there into kind of the solid tumor and even liquid tumors and mostly oncolytic and hematology areas, there's a whole host of opportunities there. We have a large pipeline that we've been working through. Well, Bobby, maybe you wanna talk about some of the different ones we're doing outside of urology space. Yeah. So, I think the key ones are, as many people maybe know, we've had an extensive experience in pancreatic cancer. We've completed a phase II trial. We have an end-of-phase II trial meeting with the FDA. The data is, I think, strong in terms of survival. They've given us some guidance on a contribution of effect type studies that we could pursue to help pursue the formal indication there. We have a trial in lung cancer. We had some disappointing results from the Lung-MAP study, where the interim, it didn't meet the interim, but we still have to see the maturity on that, because actually, what we've seen consistently is that there's an overall survival improvement when people receive N-803. We're waiting to see the maturity on that data before we can plan the next trial there. Then lastly, we're launching a pilot study in GBM. That's a study in which we actually have feedback from the agency on a pathway for a pivotal trial, but we're starting with the pilot, and then we can move forward depending on the results. So you mentioned pancreatic cancer. That's probably a good way to jump into your cell therapy- Mm-hmm. Yeah ... efforts. Maybe you could just elaborate a little bit more in terms of, like, the trial that you might need to run in pancreatic cancer to allow you to sort of move the cell therapy along with N-803 into that setting? Yeah. So the trial that we did run is a combination trial, as was mentioned at the outset. We're very focused on understanding whether or not truly innate and adaptive immune system can come together to eliminate cancer. And, you know, that's a fundamental hypothesis that we believe in. And to do that, we have N-803, that engages the adaptive immune system, but we can also provide exogenous support of the innate immune system with the off-the-shelf NK cells. So specifically, that's a PD-L1 CAR NK cell. We call the PD-L1 t-haNK cell, and that's used in the pancreatic trial. Now, if we run a separate trial where we do that as a single agent for proof of contribution effect, that might satisfy the agency. Unfortunately, we don't believe that by itself it's going to have the same clinical impact as the combination, but that's something that we're evaluating. Now, we have given over 1,000 doses. We've done that very safely, 100% outpatient, with no CRS and no ICANS. So it's a safe product. I know there's been some recent, you know, as of two days ago, some concern from the FDA regarding potential secondary malignancy. We haven't seen any of that yet. We don't expect to see that based on the way the product is made and delivered. In this last minute or so, maybe I'll squeeze in one, one more question, maybe two. I know we talked about opportunities for potential partnership- Yeah ... collaboration around N-803 and NMIBC. Just maybe a bigger picture, how you guys think about funding the business and putting you in a position to really support this launch in 2024? Yeah. So the board and Dr. Soon-Shiong himself was actually willing to step forward again and make another major set of investments in the company with the last financing round that we did. We've had both. We've been fortunate we've had both external and internal support for financing all of the efforts we've done. For a company at our size and stage, we're a large company, and that's why I call us part of an N of one. But what we do have the current financing in place to do, which really takes us all the way up through approval on those, and we sized it that way so that basically at approval, we believe there will be an opportunity for less dilutive, whether that be with a partner, whether that be with equity, whether that be with other debt or whatever it may be. And so we're, you know, we're always open to the opportunities. I've, I've never said no to a meeting to listen to somebody on what their thoughts are. But I think that's what's important, is, is that we know we've set ourselves with the runway we need to be able to get up through what we believe, this hopeful approval, knock on wood, and bring it to there. Perfect. With that, we're out of time. Thank you, Rich and Bobby, for your time and thoughts. Thanks, everybody, for tuning in. Take care, enjoy the rest of your day. Thank you.