Thank you for joining us for this Keeping It Leader event, following ASCO 2025 oral presentation of NXC-201 NEXICART-2 trial interim results in relapsed/refractory AL amyloidosis that's just concluded. Here's the requisite disclaimers, and here's the agenda for today's event. First part will be led by Dr. Raza, who will share the unmet clinical need in relapsed/refractory AL amyloidosis and current treatment options. Then we'll hand off to Dr. Landau, who will share the NXC-201 NEXICART-2 interim results she just presented at ASCO presentation. Third part will be discussing the significance of NXC-201 interim results and how this could potentially be applicable to practice and potentially practice changing. Then we'll go on to a live question and answer session. Awesome. Thank you, Dr. Rachman. I'm Gabriel Morris. I'm the Chief Financial Officer of Immix Biopharma. We are thrilled today to be joined by Dr. Heather Landau, the Principal Investigator for NEXICART-2 and the Director of the Amyloidosis Program at Memorial Sloan Kettering Cancer Center, Dr. Shahzad Raza, a hematologist-oncologist at Cleveland Clinic, as well as Dr. Jeffrey Zander, who's joining us via Zoom, who leads the amyloidosis multidisciplinary team at Barbara Ann Karmanos Cancer Institute, Wayne State University. Wonderful. With that, we will hand it off to Dr. Raza of Cleveland Clinic to cover unmet medical need in relapsed/refractory AL amyloidosis. Thank you, Mr. Morris, and thank you, Dr. Rachman. We're going to start about relapsed/refractory light chain amyloidosis patients, how we diagnose them, what are the complications they have, and how they affect the different organ systems. You know about 23,000 U.S. patients have relapsed/refractory light chain amyloidosis. They are living in the United States with currently no FDA-approved drug in this particular subgroup. Now, how the light chains deposit, or the patients who have this light chain amyloidosis, how they actually cause organ system failure. We know that our bone marrow makes these plasma cells. Plasma cells secrete these light chains. The light chains can produce, actually can cause some misfolding and aggregation. Then they're starting to deposit in different organs. We are looking for the vital organ. For example, here you can see patients with the light chain amyloidosis, they actually can cause heart failure. They deposit in the heart. Patients can have abnormal rhythm, and they can die suddenly. That's something that's scary, especially for the patients who have this light chain process. Now, this process can go very slowly and very gradually, and patients develop heart failure over the period of time. The second thing that you can see about the kidney involvement, same thing, patients can have kidney failure. Some of these patients ended up into hemodialysis or peritoneal dialysis. Also, they can also involve the liver and can cause liver failure. Now, we have seen that if you use monoclonal antibody, daratumumab, which is an anti-CD38 monoclonal antibody, that has shown impressive results in the upfront treatment of light chain amyloidosis in combination with chemotherapy and proteasome inhibitors. However, once the patients fail these therapies, we do not have any good options in terms of the treatment. Now, NXC-201 is a new innovative target, which targets against the BCMA. We already know that the CAR T-cell therapy in the plasma cells, particularly in multiple myeloma, has shown impressive outcome. We do not know that the same target, if we use the BCMA in CAR T therapy in light chain amyloidosis, would that be feasible, can give any impressive results the way we are seeing in multiple myeloma. That is a question that we are trying to answer here as well. This figure actually tells us how patients can have different complications from the light chain amyloidosis. You can see these patients can have significant severe fatigue, weight loss, or weight gain, can have lung involvement, essentially can have liver involvement, can have loss of appetite, nausea, vomiting, diarrhea, constipation, soft tissue swelling leading to respiratory failure, sometimes musculoskeletal swelling, unable to do daily routines, heart problems, kidney problems, nerve problems. Essentially, this disease is a multi-system involvement disease, can impact many organs, but particularly the heart, liver, kidney, nerves, GI. I think these are the complex issues that we deal with this disease. That is what makes this treatment quite challenging. Okay. All right. I'm trying to see. All right. We're trying to go to the next slide here. Yes. Here, this diagram actually can give you quite significant information how the heart failure actually looks like. This is the patient who has amyloid heart, like the light chain deposits in the heart and can cause the heart failure. You can see how thick the heart is, enlargement of the heart, and the heart failure. Next slide. Now, you can see if you biopsy it, you can see the amyloid fibers in it and thickening of the heart valves. That is what these light chains actually do to our vital organs. Next slide. Next slide, please. Okay. Now you can see how the numbers actually look like. Like, you know, patients who are newly diagnosed with this light chain amyloidosis, they eventually periodically progress. Next slide. Next slide again. Now, here you are seeing the existing therapies, what we have. We have a first-line therapy, which can cause the modest responses. Now, with updated data, we know around close to 60% of the patients do respond to the first-line treatment. However, when the patients fail, our options are very limited. We have a second-line treatment, which only gives you modest responses. Here you can see that the Darzalex combo in different combinations can give you decent objective response rates. When the patient fails, our options are very limited. Only a few patients, which is we are very selective in selecting stem cell transplant for these patients. Only a few patients actually are eligible for a stem cell transplant, and they have responses around 8% of these patients. Next slide. Now, we have a daratumumab-based regimen we already discussed. This is a standard of care first-line treatment for these light chain amyloidosis. Next slide. All right. Now you can see there is an upcoming clinical trial that we have long-awaited results about, using the daratumumab-based combination in combination with monoclonal antibody. Those trial results are still awaited. Next slide. Next slide again. Here you are seeing if the patients who failed the first-line therapy, what are we doing with these patients? Here our options are very, very limited. As we discussed, only chemotherapy and some other immunomodulatory agents we have, but not much options available in this area. Next slide. All right. Okay. Here you can see the first-line therapy we have, like daratumumab, but we use it in the relapsed refractory setting. We are not getting great results with these agents. The responses are very short-lasting and for a short period of time. Selected patients, and I would say it's a pretty selected group of patients, only get a stem cell transplant. Those patients do okay to a certain extent. However, the responses are very short-lasting. Now, we have a biomarker-driven drug as well, which is a target against the 11-14 translocation, which has been used off-label, and responses can go up to 40%-50% of these patients. Now, the clinical trials are also ongoing in this area where the bispecific and antibody drug conjugates have been used, and with the variable response close to 40%. In conclusion, the relapsed refractory light chain amyloidosis, as we all know, caused by the plasma cells and the light chains, which deposit in the organs, can cause significant morbidity and mortality to our patients, especially can lead to heart failure and death. This population is around more than 30,000 U.S. p atients and increasing due to increased awareness, more knowledge, and more testing. All these effects are actually improving, leading to the more incidence of light chain amyloidosis in the United States. Now, the relapsed refractory disease population, which we unfortunately do not have much options available. Physicians, including myself, we treat patients with off-label choices, and we're treating them from the therapy that what we have learned work in the plasma cells and using them. However, our complete response rates are much lower and with significant side effects. Only one therapy, only one therapy that has been approved, and it is only for the front-line newly diagnosed patients, which is anti-CD38 monoclonal antibody, daratumumab in combination with cyclophosphamide and the proteasome inhibitor, which is bortezomib and dexamethasone. That's an approved regimen in the first-line treatment. No drugs approved for the relapsed refractory population at this time. We feel that there is a significant unmet need for these patients who have a relapsed refractory light chain amyloidosis with new innovations, new target for these population. With that, I will give my mic to Dr. Landau, who's going to present the NEXICART-2 data, which she just recently presented at American Society of Clinical Oncology in 2025. Thank you. Thank you so much for the invitation to present this data. I am going to present our initial results from the NEXICART-2 study, the first and only CAR T-cell trial in AL amyloidosis. In the next few minutes, I'm going to show you that NXC-201 we have found can be administered safely to patients with relapsed and refractory AL, and that NXC-201 results in rapid and deep hematologic responses in all patients treated. Based on U.S. claims data, we estimate that 23,000 patients in the U.S. are either living with or will develop relapsed refractory amyloidosis. This population, as Dr. Raza just told you, has not a single FDA-approved drug available. He also shared that this is a disease of plasma cells that produce amyloidogenic light chains that misfold, aggregate, and cause morbidity and mortality based on deposition of amyloid in these organs, most critically when the heart is involved. Our treatment is aimed at eliminating the pathologic plasma cells and reducing the circulating amyloidogenic light chains. The anti-CD38 antibody, daratumumab, has been transformative in our patient population in the upfront setting based on the Intramedus study that showed a 60% complete hematologic response in combination with chemotherapy. That means that while that's fabulous for the patients that do respond, there's 40% of patients that don't respond ideally, many of whom will need additional therapy. Patients will relapse on daratumumab at some point and also need additional treatment options. To date, there is none. BCMA has emerged as a very valuable marker on plasma cells that has led to the approval of, it is a very valuable target in plasma cell disease biology and has led to the approval of two CAR T cells in the commercial space for multiple myeloma. NXC-201 is a unique CAR T- cell that targets BCMA. This product, this construct is theoretically optimized based on modifications in three different locations to decrease nonspecific activation, reduce cytokine release, and enhance plasma cell binding. It can be manufactured in 10 days. Based on preliminary and promising data from a trial that was designed to treat patients with multiple myeloma, but allowed for the patients of patients with AL amyloidosis to be treated, we initiated the first and only CAR T- cell trial specifically for AL amyloidosis. The study design is shown here. It's an open-label single-arm phase I/II study. Patients who are eligible are exposed to one line of prior therapy, including a CD38 antibody and a proteasome inhibitor. Patients required measurable hematologic disease based on standard criteria. We also allowed patients with a DFLC greater than 20 mg/L based on several lines of evidence that show even small amounts of circulating amyloidogenic light chain can cause organ deterioration, and suppression of that amyloidogenic light chain leads to better patient outcomes. In addition, in the relapse setting, patients who are relapsed and progressing, for that population, it is prudent to treat patients before they develop worsening organ function. Patients who received prior anti-BCMA-directed therapy, had advanced cardiac disease, or symptomatic myeloma based on CREB criteria were excluded. The primary outcome of the phase I portion of the study was safety, and the phase II was complete hematologic response based on validated criteria. The study opened to accrual in June of 2024, and we have since completed the phase I portion of dose escalation portion of the study. We treated three patients with a dose of 150 million cells and seven patients at 450 million cells, and no DLTs were observed or experienced, allowing us to progress to phase II dose expansion portion of the trial, where an additional five patients were treated at 450 million cells. This portion is still ongoing, and 25 more patients are planned, followed by FDA submission. Based on the data available as of the cutoff of April 2025, that has already been reviewed by an independent review committee. That's what informed this presentation today, and I will proceed with presenting the phase I results on the first 10 patients. Here are the patient characteristics. The median age was 67, but we treated patients up to an age of 82. The median number of prior lines of therapy was four, and 70% of our patients had already received a stem cell transplant. 70% of our patients had cardiac involvement, and while at diagnosis, these patients had advanced disease because of our practice to treat patients in the relapse setting before they progress to deteriorate to worsening organ function. You can see at enrollment, there were slightly lower Mayo stages. We enrolled at least one patient with very advanced kidney disease with significant proteinuria because we were very liberal about our enrollment criteria, and two others with more modest kidney involvement. Here are the safety data. While 80% of patients did experience CRS, it was mild, and only one patient had grade 2. It also occurred early and was short-lived because we used the prompt administration of tocilizumab at the first sign of fever. We saw no evidence of ICANS or any neurotoxicity of any kind in any of our patients. As expected, neutropenia was seen in the majority of patients, but there was only one episode of febrile neutropenia, which was not associated with an infection. Not unexpectedly, our patient with advanced kidney disease developed worsening kidney function shortly after the CAR T-cell administration and became dialysis dependent. However, she recovered from her CAR T-cell hospitalization and was back to work tolerating hemodialysis when she later presented with a dialysis catheter septic event, which was eventually complicated. At five months post-CAR T-cell administration, she died of a secondary infection, unfortunately. We had two others develop grade 3 infections that were easily managed with IV antibiotics, and there were no unexpected or lasting cardiac toxicity. Here are the results of the data cutoff with a median follow-up of approximately four months and our longest patient out 10 months, actually now 12 months. You can see on the left the waterfall plot that depicts the percentage change in the DFLC or the M-spike from baseline. And all patients' disease marker normalized with a median time to first response of seven days. As in other CAR T-cell trials, we see that the immunofixation may persist for longer. On the right, you see a line graph that shows the prompt reduction of patients' paraprotein into the normal range, which was associated with organ responses. And we saw two cardiac available patients have a cardiac response. Two of our renal available patients also respond between one and four months after CAR T-cell administration. Of course, there was one patient who had renal progression that we discussed, but there have been no cardiac progression events. One patient who came into the trial with fairly symptomatic cardiac disease gave us an account of her experience. She wrote, "One week since I left the hospital at day 10 after those magic CAR T cells, I've been very comfortably walking two to three miles a day, even on inclines. I never thought I'd be feeling this strong and vibrant just 15 days after my CAR T-cell infusion, nor did I ever guess that I'd be experiencing less of that horrible leg fatigue, shortness of breath, and chest tightness that was ever increasing and weighing me down for the months preceding this. This just proves that this treatment for her was very clinically relevant and made a clinical difference. Here is the hematologic responses as reviewed by the independent review committee and the swimmer plot showing the duration of those responses. Seven out of 10 or 70% of our patients achieved a complete hematologic response, which was our primary efficacy endpoint. However, the three who have not yet achieved a complete hematologic response only have not because their immunofixation remains positive. However, in the bone marrow, those three patients are MRD negative, and we expect that the response will deepen. There was one death that we discussed unrelated to NXC-201 at five months following treatment, and there have been no hematologic relapse or progressions to date. In conclusion, in this patient population who has a true unmet medical need, all patients received treatment in 14 days. CRS was mild and manageable, and there was no neurotoxicity of any kind. All patients experienced rapid and deep hematologic responses with a median time to first and best response of seven and 26 days. Eight out of nine available patients were MRD negative at day 25 post-CAR administration, and 70% of patients at this early time point achieved a complete hematologic response, but we expect that to evolve. Organ responses were documented in four out of five available patients, and there have been no hematologic relapse or progressions. This multicenter trial is ongoing and continuing to accrue. We look forward to further results in the future. I thank everybody who participated in this study and you for your attention. Thank you, Dr. Landau. Thank you, Dr. Raza. We will open this panel for discussion. Dr. Zander, thank you for joining us today. If I may hand off for all three of you to discuss the significance of these results and potential practice applicability. Would you like to share a few thoughts, Dr. Zander? Yes. Can you hear me okay? Are you able to hear me? Are you able to hear me right now? Yes. Perfect. I think the results are extremely encouraging. One of the main concerns I think many of us in the amyloidosis community had about CAR T- cells would be whether cytokine release, CAR T is frankly in bispecifics, right? Whether amyloid patients with cardiac involvement would tolerate cytokine release. This study has shown that that is a manageable potential complication. It's a manageable symptom. I mean, I think it does require close attention to patients and prompt initiation of treatment. With the strategy that we've been employing in this study, we've shown that we can keep cytokine release to be a very manageable symptom that patients ultimately don't struggle with greatly. The other thing that's so encouraging just from a safety perspective is so far we haven't seen in this study, or correct me if I'm wrong, but in the original myeloma study that included amyloid patients, we're not seeing the neurotoxicity that we've seen with some other products. I mean, from a patient standpoint, I think neurotoxicity, particularly delayed neurotoxicity, is often cited as the reason they're ambivalent or nervous about pursuing CAR T-cell therapy. That's also, I think, an important finding from this study that the neurotoxicity has been very manageable. The last thing I'll say before I turn it over to our colleagues there live at the panel, both the speed of manufacturing and the speed of response, right, I think eliminates the last major concern that many people might have about CAR T as a therapy for amyloidosis. Unlike myeloma, we don't tolerate hematologic progression, biochemical progression, right? That's an indication to resume therapy because by the time someone's developed symptoms, you've sort of missed your window of opportunity to prevent those organ events, right? Having a therapy like this where manufacturing can be very abbreviated compared to what we're used to with CAR T, and then not only fast sort of vein to vein, right, collection to administration, but then a fast response within just sometimes as short as a week after the initiation of therapy, we can address that rising light chains quickly and minimizing the risk of progressive organ dysfunction. That's my opening volume. Thank you, Dr. Zander. I think Dr. Zander touched on a few points that I'm sure you'd like to address. I think Dr. Zander made excellent points. I mean, this is what exactly the physician, we also think the same thing. Now I'm going to give you a different perspective. Let's say I'm a patient and I'm going to my doctor and ask him, "Okay, give me a therapy for this type of disease. I have it. My light chains are going up. What options do you have?" Now, as physicians, when we see these patients, we offer the first-line treatment, which is our standard of care that we have mentioned. It's a great drug. I mean, the four-drug combination, 60% CR. Those patients who have deep hematological responses are the ones they live longer. Their organs recover happen. They have better organ responses. It is one of the recognized markers for us to understand the efficacy. I know a lot of studies have been done looking at monoclonal antibody targets and different ways of targeting it. If you ask me, what is the recognized marker that you look for? I like to suppress the light chains. This is what my marker is. The second question comes up, "Okay, you have a therapy which can suppress the light chains. Is it safe?" I mean, it's a very important question. Particularly, this trial is actually answering this question, although it's early preliminary data, but you can see how quickly we are getting the suppression of the light chains. I think it's from the patient perspective, it's a big thing. Like day seven or maybe in a month, you are seeing excellent results. The light chains are going down. That is very appealing for these patients because when the disease does not respond well to the first-line treatment, the numbers come up. I do not think we have really good options for these populations. You are looking for a safe and you are looking for efficacy point standpoint. The third point, I think that is an answer we need. It is the durability of the response. If you look at it, our multiple myeloma patients, their durability is excellent. Patients are living longer and they continue to have sustained responses. We have now five-year plus data that patients have been doing well on CAR T-cell therapy. I am hoping if this is all in the moving forward, we show the durability of the response thing, I think a lot of patients would benefit from this type of therapy in the future. Just to add what my colleagues have described, I think that the biggest takeaway from this, again, not only the safety, this safety and the rapidity of the response, but there is so much value in the one-and-done approach. I mean, these patients who do not respond to their upfront therapy in particular continue to go on suboptimal therapies that are toxic and prolonged because they never get deep responses. If you do not respond to Darzalex-CyBorD and you go on to one of these other approved drugs for myeloma, number one, you will ultimately have toxicity. Number two, there are very few complete responses in that situation. These people end up on Immids or carfilzomib or all of these different treatments that have significant toxicity because we have nothing else, or a stem cell transplant, which as somebody who has been treating amyloid for my whole career and very comfortable transplanting patients for this disease, I can say that this treatment is a whole lot easier and a whole lot more effective than stem cell transplant. Hands down, I would easily choose this over a stem cell transplant in terms of recovery for the patient and rapidity of response. The patients are done. They are grateful. I can tell you that patients number one, two, and three in the trial are almost 12, 11, and 10 months out and living their best life. Glad to hear that. Thank you for sharing your thoughts. I would like to add one interesting thing about this study that some of these patients have stem cell transplant and they fail the therapy. And post-stem cell transplant, the CAR T-cell, this NXC-201 has shown amazing results. So that's a plus even after the stem cell transplant, the patients fail. This therapy actually gives good results. Would you like to share any additional thoughts or comments? If I could speak. I agree with the other speakers. I do think that in terms of durability of response, I mean, just based on plasma cell burden and also plasma cell biology, I mean, I think we know from other treatments like transplant where responses can be quite extended without the need for maintenance therapy. Also, non-transplant therapies like daratumumab, where the single-agent response rate is quite a bit higher than you would expect it to be in multiple myeloma. I think that there's reason to believe that the durability of response to this therapy will be at least like what we see in myeloma. It might be significantly longer than that. I mean, that's going to be sort of the exciting thing to see is what percentage of patients are still going to be having ongoing responses. That said, the other thing that we do need to keep an eye on over the coming year, right? We need to see, we know from our experience in myeloma and with other BCMA-targeted therapies in myeloma and amyloid, frankly, we know that hypogammaglobulinemia can be a very prolonged and persistent issue. Infection risk, I suspect we're not going to see a rise in infections as we go, but we may see a persisting risk for infections. That is something we also are going to have to pay attention to as we go forward with these patients. That might end up being something that requires ongoing management even while they're still having a hematologic response. We'll see. Yeah. I do think that it's encouraging that this product in the myeloma space and in the previous reported data from the amyloid patients have not shown any neurotoxicity or any prolonged neurotoxicity. Again, that is something that we'll be watching closely as well. Very encouraging that there has been no evidence of that in the first 16 patients treated in the Israeli cohort or our first 10 patients who were treated with 12 months of follow-up with the first patient. Certainly, that's a growing concern in patients treated with Carvykti these days. Thank you for sharing. Perhaps our audience would probably love to hear your thoughts on how you see this fitting into your practice and where you see this fitting into the landscape of relapsed/refractory AL treatment. I think I will always offer our first-line treatment, which is an FDA-approved therapy like a Darzalex-based combination as an upfront treatment. Those who do not respond, I will offer them this therapy as a second line. That's my personal choice. I would agree 100%. We just do not have anything else to offer, anything that is anywhere close to efficacy in this space or less toxic, to be honest. Dr. Zander, would you? Yeah, I agree. I mean, this looks extremely promising. I mean, if it becomes an FDA-approved option, I mean, for starters, it would be the first approved therapy for relapsed amyloidosis. I think it becomes a top consideration for relapse treatment. Based on the patients that are being included in this trial, we will have some information about treating older patients, treating patients with borderline cardiac function, borderline renal function. I think it's hard to—I think it'd be hard to make the case, for instance, that transplant would be an easier or more effective therapy if the numbers, as we're seeing them right now, hold up both in terms of safety and hematologic response rates, which have been uniform and deep on this study so far. I mean, I think this becomes a top consideration. I think the harder—the only thing I would say, though, just a word of caution because the data is still fairly early. The one thing that we see with transplant is durability, right? For a patient, we're going to need to pay attention to how durable these responses are because for a very fit patient who has relapsing disease, particularly one who does not have cardiac involvement, transplant may remain a very good option for such patients based on the durability of responses. We'll just have to see. We'll find out. Right now, this certainly does look awfully promising. Thank you for the very thoughtful discussion. Perhaps we'll open up the line for questions from our audience and our moderator, Mike Moyer. Great. The first question was really just thinking about the total market opportunity. How many patients ultimately do you think could be treated in the U.S. with NXC-201, the CAR T therapy? I know Dr. Landau had opined a little bit on the incidence prevalence rates, but kind of how do you guys think about relapsed/refractory AL amyloidosis in terms of just the size of the number of patients and the unmet need as you've been discussing? Again, I think based on the claims data and the fact that there is not a single other drug available for this condition, that at least 20,000 patients exist who could benefit from this treatment at this time. Probably more in the future as more patients are living longer with this disease and hopefully not dying suddenly in the upfront because of the potential for, I think, recognition to get better, especially since there's been new approved drugs for TTR and now cardiologists are getting better at making the diagnosis and more recognition when we have more treatment options available. Hopefully, patients will be diagnosed early, but it does not mean that they will respond any better to the upfront therapy. They just hopefully would not die of sudden cardiac death, and that would allow more patients to be treated who are not responding to Darzalex-CyBorD or who relapse thereafter. Yeah, I agree. I just want to add one more from the patient perspective. This is a one-time therapy. When you give upfront treatments for several cycles and then maintain them, you will find here some of the patient preferences, like, "Do we have any alternatives available? Any other therapies available that can be done?" I think this will be an option for relapse patients. I believe 50%-60% of the patients eventually need some additional therapy. Now in an academic setting, we are seeing already patients who are second line, third line, fourth line. The pool is quite big, especially those who are coming to academic centers or amyloid centers where they are offered other therapies. Now, as a regular—I mean, in the physicians who have been seeing in the community, they are treating it as a first line. They have 50%-60% patients do well on Darzalex, CyBorD-based regimen. In academia, I think the numbers are more. We are seeing relapsed/refractory cases. This is an excellent option to offer to these patients if this therapy is FDA-approved. Dr. Zander, any comments on this question? I do not have an awful lot to add. I think the attractiveness of a one-and-done treatment is obvious. Again, especially if it does not turn out to have any long-term toxicity, right? It ends up the responses are durable, and toxicity is mostly restricted to the initial post-treatment phase. I think that it's going to be a very, very attractive option compared to, frankly, even other BCMA-targeted therapies, right? I mean, the one-time treatment is just a super attractive thing for patients. Hopefully, we'll continue to see the safety profile that we've seen because I think there is an understandable reluctance in the patient community to pursue high-dose chemotherapy. I think this might be something that will get maybe more traction amongst patients than high-dose therapy. Yeah. Question that I often get, and I think all of us who treat both amyloidosis and multiple myeloma is, "What's the benefit of a CAR T- cell versus a bispecific antibody?" Given the fact that bispecific antibodies are off the shelf and they have, I would say, pretty similar safety profiles, with the most significant issue, the upfront risk of CRS. I would say really what we're learning in the myeloma population, I think that if you ask any of the myeloma doctors, if you have an option to treat somebody with a CAR T- cell and you don't have to go for the off-the-shelf, you have the ability to wait for the production in that space. So far, it's been a six-week lag time, I would say. Then all of us would prefer a CAR T- cell over a bispecific because of the one-and-done approach. If you have that ability, we're certainly grateful for having the bispecifics to be on hand immediately. They are, although in the myeloma space, a little bit less effective, but they are available. It has been a significant improvement for that population. However, there is the issue that if you have a bispecific, which is ongoing therapy and continuously, it's a continuously using T cell redirecting therapy, then at the time of relapse, the efficacy of a CAR T- cell after a bispecific antibody is pretty low. Whereas the converse, if you treat somebody with a CAR T- cell, you still have the option to treat patients in the future with a bispecific antibody. That is also from a sequencing perspective, quite attractive. That is another question I'm often asked. Yes, it's important to have bispecific antibodies. They've provided quite a bit of value, especially in the patients that can't wait for the manufacturing time. Now, if you have the option to do a CAR T-cell, especially in 14 days, none of our patients required any bridging therapy. I would assume that nobody will moving forward. That's a whole game changer in the field. I agree. We divide them into fit, unfit, and frail. This is in the myeloma communities. If your patient comes in and you think the patient is fit and you want to decide to give CAR T versus bispecific, I would go for CAR T for these patients. However, the myeloma CAR Ts, which are approved, have side effect profiles compared to this. There are different trials, but I've been seeing problems from the CAR Ts that are approved in multiple myeloma, especially the neurotoxicity point. I want to highlight that because we are not seeing that particular effect. Many times when we offer myeloma patients CAR T, one of the denials from the patient's side is risk of neurotoxicities. "Oh, I don't want this particular side effect." We are not seeing this with this agent. I think knowing that amyloid population is mixed, like they are also some of these patients are frail and some are fit. This gives us an option to even use the CAR T even in frail patients, especially with a reasonable toxicity profile that what we are seeing it. I think if I have two options, bispecifics and CAR T, and both are approved and I need to pick one, I would still go for the CAR T option, one-time option, sustainable durability of the response. That's what we like to see. Infection risk that we are talking about, bispecific, you keep it going every two weeks, every month. Here you have a fixed duration of therapy, and then you watch them and give monthly immunoglobulins to these patients to control the infection risk. My always take is in amyloid setting, I would prefer the CAR T for these patients if they are fit or unfit. The frail population is the only one that got significantly frail. They have significant heart problems, significant liver problems. We have also excluded these patients from this study, especially the advanced heart failure patients. Here we have to be very careful and cautious and looking for some less intensive therapy for these patients. I think both of you raised a couple of important points and probably anticipated a few questions that might have been on the list, Mike, especially how bispecifics and others fit into the landscape. Sure. I think to that point, one of the questions was, in time, could NXC-201 be used in earlier lines even before Darzalex? Kind of how do you think about that in time? I think we're going to have to see the long-term durability of, again, the Andromeda study and this experience because if we now were just showing the CARTITUDE-1 study that shows a third of patients are now with very refractory disease are five years out with no relapse or progression, that speaks to long-term remissions. I don't know if that's going to be the same with Darzalex-CyBorD versus the CAR T-cell. Again, I think we get very, very deep remissions on the level of what we see with transplant. We know patients with transplant in the upfront setting can go decades. I think it is going to be about the durability and our comfort level. Of course, in the upfront setting, patients are actually sicker in the upfront setting, so we would have to be very mindful of that. It may be the potential to get a very deep and rapid response, but you would have to—the supportive care aspect of the treatment has to be well thought out before moving this into the upfront setting. Certainly, if somebody—I mean, I think quickly, if one month, two months of Dara, patients do not respond or are unfit for the chemotherapy, this can be used quite readily. I would like to just echo Heather's comments a bit. I mean, Dr. Landau, I think, astutely pointed out these newly diagnosed patients, right? This is a different patient population. Studies like this one, any study in relapsed amyloidosis is selecting for survivors in a sense, right? The patients who are at most risk of cardiac death have survived that highest risk period and are now able to participate in studies for relapsed disease, right? There is a durability question. If you're thinking about patients who are potentially transplant candidates, and then there's safety that you need. I mean, I think based on the data we're seeing, the efficacy data, it's actually highly likely that this therapy would have a higher response rate than Darzalex-CyBorD. I mean, I think that's actually likely. In terms of, is it as tolerable therapy in that patient population as it seems to be so far in the relapsed patient population, I think remains to be seen. To replace Andromeda-based therapy upfront, I think you'd have to head-to-head show that you could beat it. I don't think that there'd be a lot—I think it would be hard to recommend off-label use of this upfront, certainly, until we have data showing you can deliver it safely and effectively in that patient population. Great. I think fantastic discussion. Mike. Another question coming in. Just in terms of the potential, just given the safety profile, if this could potentially be an outpatient CAR T, if so, what might the process be if approved? What would the rollout look like? What will the important steps for adoption be? Just to repeat the question, the question was, if the safety continues to be conducive to outpatient administration, what would the rollout process be for such therapy, for such outpatient CAR T therapy? I definitely think this could be an outpatient therapy. I think that we're already keeping patients in the hospital too long. The CRS is very quick and very brief. Erring on the side of caution, we keep people in for 10 days. There is almost no one, very few patients who really needed that level of care for that long. I think that we're very comfortable doing CAR Ts as an outpatient. I think it would be prudent based on the early and quick CRS. Either what we do in other settings is either do the lymphodepletion as an outpatient, admit them day minus one, give the CAR T cell. If day plus three, they don't have any CRS. Or we remotely monitor these patients as long as they're close to the hospital. We do that in other CAR T-cell settings, use remote monitoring, and admit them at the first sign of CRS, which is probably very doable. We've been keeping the cardiac patients on telemetry, which we're used to doing. I would probably continue to do that just because in the setting of CRS, patients who have already had paroxysmal AFib may develop paroxysmal AFib, not that they need to be treated for it or anything. That would be one concern in the cardiac patients just during that kind of three-day period of CRS. I think 72 hours makes sense to us only because these patients, many of them have cardiac involvement. You want to make sure arrhythmias and things can be watched. It is a new product. You want to learn even in a larger population, more broad safety. You really need it in a larger number of patients that are doing okay. What we have learned from myeloma CAR Ts, we initially started patients, everybody got admitted in the hospitals. We learned predictable CRS are happening after day five or day six. We keep everything outpatient until day five, and then we start to admit patients from day six to day ten. We cut down their hospitalization from other CAR Ts from 10 days to five days. Bispecifics, same thing we learned. Initially, we admit everybody, learning about CRS can happen, these side effects happen. Now we learn it is manageable, can be done as an outpatient. Why not about this product? I think this is even showing much more safety and very predictable CRS episodes. And even if it's happening or it's not happening at all. I think we can manage them. The more we learn, the more we will be confident in doing it as an outpatient. Wonderful. Dr. Zander, your thoughts on potential applicability of outpatient CAR T? Oh, I don't think I have anything to add to what the other speakers said. I mean, I think that at most, a very brief hospitalization would be required. The time in the hospital under any circumstance, whether I think there are going to be some centers that are better suited for doing this fully outpatient, and then other centers where they'll need to be some brief time in the hospital. In any circumstance, it's not going to be like what we do with, for instance, transplant. It's not going to be like that. It should be shorter. Perhaps we'll take one or two more questions, Mike. Just one last question, Ilya. What catalysts with the NEXICART-2 trial should investors be paying close attention to over the next 6- 12 months? Wonderful question. Would you like to comment on that? Sure. I'm happy to take that. Again, thanks, Mike, for coordinating the Q&A. Thank you to our panelists. I think we're approaching the end here. Maybe if you have any other questions, we can do one more clinical question. We're excited about the NEXICART-2 trial. As folks have seen, Dr. Heather Landau, our lead PI, presented at ASCO this year. We've presented the first 10 patients in that trial. We are working on completing enrollment in that trial and submitting a BLA. Between now and early next year, that event will happen along with the final readout. Dr. Rachman, anything to add? No, that is exactly correct. I mean, look, we're excited to be here. The investigators, patients, teams have done an incredible job of advancing this therapy that we believe might be groundbreaking therapy for this disease for the population that terribly needs better standards of care. That is what we are looking forward to. I think this year is going to be the year of bringing this forth. I would just add to this forum, I would just throw this out there because as we're looking for other populations who could benefit, if there are patients who have other underlying B-cell clonal diseases with amyloid, those patients also have a very unmet medical need. I would say exploring this therapy, which is safe and effective in other areas of unmet medical need, like MIDD, like lymphoplasmacytic lymphoma with amyloid, where we really do not have therapies. All of the therapies in that disease only get to partial response. That is okay for the LPLs in general, but not the LPLs with amyloid. There are other opportunities to use this in patient populations with unmet medical needs. Really, very good points. I think myeloma-associated amyloidosis, a lot of these patients are excluded from the studies. I think that is an area which we really need to take in attention, that those who have both diseases together, how are we going to manage them? I would step forward. I also think that companies should explore options in multiple myeloma. I mean, that is what I think. All right. That is my two cents. Thank you. Dr. Zander, any concluding thoughts? No, I mean, I agree that there are other sort of difficult-to-treat plasma cell disorder patients who do not have any particular approved options. All of the MGRS patients, for instance, many of whom have some of the same issues related to nephrotic syndrome that amyloidosis patients have, light chain deposition disease patients. They may also have very impaired creatinine clearance. That is a patient population, a fairly fragile patient population who might be able to benefit from this. I do agree with that. We already have efficacy data in myeloma. It would be—I mean, ideally, amyloidosis with or without coexisting multiple myeloma would be a potential way to use this if the data in straight amyloidosis holds up. I know that you're going to explore all the different ways that this therapy could be beneficial to patients if we can get it across the finish line in amyloidosis. Including remarks, I would just like to express my deepest appreciation for the dedication that our investigators exhibit every day, driving innovation and improvement for standards of care for their patients. We're truly honored to partner with you on this mission. Thank you for joining us today. Thank you, Dr.