Good evening, I'm Rami Elghandour, I'm the Chairman and CEO of Arcellx and it is my privilege to welcome you to our investor relations event here in Milan. Thank you so much for those who joined us in person. You get extra credit and thanks as well for the many of you joining via our webcast. Before we get started, a look at our forward looking statements in terms of our program for this evening. I'm going to kick things off by sharing a little bit more about why we're building a different kind of cell therapy company. I then have the pleasure of welcoming Dr. Kaur to the stage. She'll share the latest results from our registrational Imagine-1 study that has been selected for an oral abstract presentation here at EHA that she herself will be presenting tomorrow at 5:00 P.M. Dr.
Chris He, our Chief Medical Officer, will then lead a physician panel and he'll be joined by both Dr. Kaur as well as Dr. Patel. Dr. Kaur joins us from Mount Sinai and Dr. Patel from MD Anderson and we're very much looking forward to hearing their wisdom and insights. Lastly, we'll open it up for your questions. As I mentioned at the outset, we are building a different kind of cell therapy company. We endeavor to match the clinical differentiation that you've seen from our anito-cel program with operational and commercial excellence in execution. I'm really excited today to share with you a little bit more about our plans and progress as we gear up for our anticipated launch of anito-cel in the United States in mid to late 2026. First, a quick look about how we got here.
Arcellx was founded around the principle of addressing some of the limitations with biologic-based binders and we have developed the D domain, our proprietary novel synthetic binder through which we have been able to demonstrate what we believe to be a best-in-class profile in myeloma. That addresses both the primary limitations that we see with biologic-based binders, which are namely safety and scale and reliable manufacturability. We have leveraged this binder to generate what we believe is the strongest data set in the relapsed and refractory myeloma population. When you look at the profile of anito-cel, combining the efficacy, safety, and again that scale and reliable manufacturability with Kite, the leader in cell therapy, we believe we can have a huge impact for the multiple myeloma community and build a significant business. We also believe in leaving a lasting legacy.
If you've been following the CAR T space over the last couple of years, particularly over the last four years, you know, it's been a particularly challenging space, both from an entrepreneurial and as well as from a public company perspective. That challenge has existed despite a significant amount of clinical success. Broad based business success has been harder to attain. We are committed to proving that you can build a meaningful business in the CAR T space by doing the good of helping patients. That starts by focusing on areas of high unmet need. Certainly we believe myeloma is one of those spaces. As we've shared with you before, we believe that the second line plus population or second line plus market for multiple myeloma is $12 billion.
As these therapies advance into frontline, which we believe they will, that market is sized at approximately $20 billion. Importantly, the fourth line plus population is approximately $3.5 billion. The reason that that is notable is that we expect to launch in the fourth line plus population again in mid to late 2026. How do we arrive at these figures? For the first time, we're going to share a little bit with you about how we've built our models, some of our assumptions into our launch, and some of our pillars of launch going forward as we approach again, this commercial launch in 2026. This is that first piece of information. If you look at this, the first starting point for us is assigning class share for myeloma CAR T's across different lines of therapy.
You can see that there's a range in those class shares that ascribes to the two different market opportunity sizes that you see here. The first one, that is $9 billion, is based on the currently approved therapies for myeloma, excluding anito-cel. The $12 billion figure is inclusive of anito-cel in 2028 and beyond. One of the primary differences between these two market estimates is actually our Imagine 3 trial. There are two distinct features in Imagine 3 that we believe will help drive this market, help us help a lot more patients, and generate this greater market opportunity. The first is that Imagine 3 is a dual exposed population. Specifically, it is an anti-CD38 IMiD exposed population that is different than some of the labels that exist with current therapies. Specifically, for example, a len-refractory PI exposed population.
That difference in population, we believe, can lead to a sizably larger population. To address the second difference is that Imagine 3 has a contemporary control arm, meaning that in the control arm there are multiple DARA regimens that we believe are going to be critical in driving engagement in the community physicians and again expanding the patients that can benefit from these therapies. Digging a little bit deeper, we're going to share with you some of our primary market research, and this is fairly substantive market research that included over 300 hematologists and oncologists over the last two years.
You can see here, including treaters and referrers in this research, that the market share assumed, and this is peak share, not necessarily penetration as of today, but the peak share assumed with the existing class of therapies can go up substantially in the future with the introduction of newer therapies like anito-cel, for some of the reasons that we discussed. You can also see that the share in that future case is fairly consistent across our studies in terms of that substantial increase, whereas the share for the existing therapies fluctuates a bit more. We believe that's a function of the in-market experience. Some of the things that we've all heard about in terms of delays and toxicities that may be impacting the in-market experience and causing greater fluctuations in those assumptions in totality.
You could see, however, that anito-cel can drive significant expansion and we believe it will help expand this market and again expand the number of patients that can benefit from BCMA CAR Ts. We spent a lot of time talking about how we've arrived at this market, its size, the class share assumptions. Let's dig a little bit into how anito-cel itself performs within the BCMA class of CAR Ts. You can see here again citing our 2024 research, that anito-cel garnered a 58% market share both in our qualitative and quantitative elements of our research, and that increased substantially to 83% in our 2025 research. We believe that increase is really reflective of the profile that you saw in our Imagine 1 results, which again, Dr. Kaur will share a little bit later today.
Specifically the replication of the efficacy profile in our phase one, which led to a north of 30 month PFS as well as the safety profile where we again saw no delayed neurotoxicities in a patient population that's approximately three times the size of that of our phase one. It's also really encouraging to see that the patient research led to an 83% share. Coincidentally as well, we know we live in a world where patients increasingly are taking more charge of their journey, of their treatment options. Having this level of patient advocacy we believe is going to drive a significant role in the adoption of anito-cel. Two other things I want to mention.
The first is if you think back to those share assumptions that we talked about, they still account for a significant amount of alternative therapy use, whether they be bispecific or otherwise, while still resulting in significantly large markets in the myeloma CAR T space. However, we also expect that the CAR T class share in myeloma will continue to increase because of the unique durability and particularly the quality of life elements of CAR T therapy. Now, everything I've showed you so far relies on asking physicians to look at different profiles and ascribing share based on these profiles. They see whether in the present moment, again with only the existing therapies or a future time point inclusive of therapies like anito-cel.
Another way you can ask this question is to simply ask them, based on this profile, what is your likelihood of prescribing and what is your motivation of prescribing this therapy? You could see that stands at 90% for anito-cel. The reason that question is important is we know with anito-cel the ease of delivery and use, given this, the safety profile, the combination with our partners at Kite, who are the best in the world at what they do in terms of delivery, it's going to be a therapy that the more you use it, the more it's likely going to be adopted. This is a really important data point for us informing our launch decisions.
I think I can summarize that this is a very large and expanding market, that we expect a significant class share for myeloma CAR Ts and that within that class, anito-cel is poised to be the leading CAR T therapy. That informs our launch decisions. The first pillar of our launch that I want to share with you is how we expect to expand into the U.S. ATC market. We expect to launch into 160 ATCs in the United States within our first year of launch. You can see how substantially different that is from prior myeloma launches. The reason for that, again, is that market research that gives us the confidence that this is a highly desired therapy that is likely to be rapidly adopted.
Now, part of the reason that these historical launches have been staggered is because supply has been a significant challenge. The second pillar that we want to share with you is that we're planning to have manufacturing capacity to capture the majority of the fourth line plus population at launch, scaling to be able to cover the entirety of the fourth plus line population in 2027 with a global potential of greater than 24,000 doses within the Kite network. Now you're going to hear from some physicians later today and I'm sure they will tell you that capacity just isn't it. There are other challenges that impact adoption of these therapies. Turnaround times, inspect out of spec rates, and logistics and planning. Let's talk about those things. We expect a turnaround time of less than 17 days with anidocel.
What's great about where we are today is that Kite has been able to deliver on that. We've shared this previously that we are seeing a less than 17 day turnaround time with anito-cel in Imagine 3. This isn't a hypothetical, this is a real operational achievement that Kite has been able to deliver. In terms of in-spec rates, Kite's in-spec rate I believe is somewhere around 96% and we expect a similarly high in-spec rate once we are commercial. The other element that's going to be really important is that we're really excited to share that anito-cel is going to be part of Kite Connect. Kite Connect is the leading platform in cell therapy in terms of patient onboarding, tracking and logistics. It reduces significantly the friction of the adoption of these therapies. We are introducing a new therapy to the market.
Imagine introducing it in a way that does not just take physicians to something that they are used to, but something that they yearn for, that they are excited for, that they want to use because it helps them run their programs in a much more efficient and reliable manner. We also wanted to share with you what this launch is going to look like on the ground. While myeloma CAR Ts have been on the market now for three years, amazingly there are still a number of centers that have not had access to these life saving therapies. We are excited alongside our partners at Kite to be the first company that can bring these therapies to these patients and particularly not any therapy again. Anito-cel with its unique profile across safety, efficacy, and scale manufacturability.
We're also really excited to share that we are very ready to take this market with our partners at Kite, working together to bring a best in class experience and service. When you think about Kite, you think about the brand, you think about their expertise. And with Arcellx we bring a knowledge of this particular agent and a focus and a track record of execution that I'm confident together we are going to be the best in class service organization alongside the best in class CAR T that we're looking to deliver. Now again, to recap, we've talked a lot about the size of the opportunity, the class share, the specific anito-cel share, some of the elements that are going to drive the launch from supply to ATC, onboarding to Kite Connect. Let's spend a minute on market access.
We are in the process of initiating our preapproval information exchange which we believe will allow us to have access to 80% of covered lives within 30 days of launch and 90% of covered lives within 90 days of launch. As you'll see, that'll continue to tick up towards that 99%-100% level over time. It's also worth mentioning that the payer mix for BCMA CAR Ts is not too different. It's actually quite similar, maybe a little bit favorable relative to the more broad myeloma therapy payer mix. The reason that's important is that it means that there aren't any payer issues that are significantly skewing the payer mix, which tells us that there is generally access to these life-saving therapies for the patients that need them.
All right, so let's shift gears a little bit and talk about what I said at the outset, which is the type of business that we're building. When you look at the capital that we've raised over the last couple of years, we've been public since February of 2022 and you look at how much of that remains on our balance sheet as of Q1, which is $565 million, over half of that capital. When you look at that relative to the achievements and the value that we've been able to create, and relative to our headcount, approximately 170 team members, that really speaks to our operational differentiation. We talk a lot about people, culture and specifically diversity as our superpower and what makes us different. You can see that reflected in how we operate our business. That also informs how we think about the future.
We expect gross margins that are greater than or equal to 70% at launch and we expect to reach profitability at less than $1 billion in anito-cel shares. Now, a big component of our differentiation certainly is our partnership with Kite. This was really a win win deal and partnership with Kite. They are able to drive this myeloma therapy through their infrastructure and through their expertise, which is incredible for patients and physicians and for their organization and we're able to leverage that infrastructure as well. Mainly it reduces cost of goods for us and eliminates capital expenditures in a way that again helps us achieve significant margins at the time of launch and to drive profitability in the near term.
I will say also going back to what I said at the outset, that it is really important that certainly our mission and why we all chose to be in oncology is to make a difference for patients. We could have chosen a lot of different fields. We chose this even though it's hard sometimes because ultimately we want to do something that makes the world a better place. It is also really important that we build good and meaningful and valuable businesses because that will help drive more and more investment into this category that I believe will be a forward pillar of medicine. This is certainly important for Arcellx, but again, from a legacy perspective for us it is informing a hopefully more and more attraction and investment in this space.
Lastly, before I wrap up, we do want to share with you an illustration of how this all comes together. We have put together this illustrative P and L in a future state when we achieve, and we hope to achieve, $1.5 billion in sales. You can see through this example that we get incredible leverage from both due to our commitment to operational excellence as well as our partnership with Kite that drives significant variability. To orient you to this graph, you can see the shaded portions are the range for each of these bars and particularly the profitability bar you can see there at the end. That is compared to a cell therapy peer at a similar stage. You can see the differential in the overall profile as well as in the profitability line.
With that, I'd like to conclude with sharing that anidocell is expected to be the preferred CAR T. Based on our experience, I can tell you that I've conducted and our team has conducted this type of research in the past for other launches and it has been incredibly accurate and instructive. We're very confident in it and as you can tell, it informed a lot of our commercial decisions. We do expect anidocell to expand the market for the reasons that we shared. We're expecting a broad launch based on the combination of the belief in these two attributes. Hopefully today, you know, we have incredible confidence in our therapy and our clinical differentiation. Hopefully today you got some more belief into why. We're also incredibly confident in our commercial plan and our execution.
We will launch with the excess capacity we need to address patients and to make sure this life saving therapy is available to as many patients as can benefit. This is a different kind of company. I know a lot of you get the opportunity to interact with some of our team, but it is really, truly a super team. It is an honor and a pleasure to get to work with them every day and we are committed again to bringing this incredible therapy to as many patients as can benefit and building a differentiated company that we certainly really value being a part of, but can also help drive more investment and attraction to this incredibly important space. It is my pleasure to invite Dr. Kaur to share the latest Imagine One data.
Thank you everyone for having me. My name is Gurbakhash, I'm from Mount Sinai Hospital in New York City. Before I delve into the phase two portion, namely IMAGINE-1, I'd like to remind everyone of the phase one study and the data in the phase one study of 38 patients there was an over 100% overall response rate and 79% complete response that was observed at a median follow up of 38.1 months. Anito-cel achieved a median PFS of 30.2 months for patients and a complete response or better in 79% of the patients. Median overall survival was not reached and the highlight is that the safety profile of this CAR T product is predictable and manageable with no delayed or non-ICANS neurotoxicities including no Parkinsonism, no cranial nerve palsies and no Guillain-Barré seen till date.
This is an overview of the anito-cel imagine-1 phase two study design with patients which is pretty standard for this patient population. 129 patients were enrolled and ultimately 117 patients were dosed with this product. Anito-cel was successfully manufactured in 99% of the patients. These are the demographics of the patient population enrolled onto this clinical trial which is on par with CAR T products at a similar stage of development. Now in terms of efficacy, at a median follow up of 12.6 months the overall response rate was 97% and the complete response or better was seen in 68% of the patients with the VGPR, which is very good partial response or better, of 85%.
The median time to first response was one month and in the myeloma world we often evaluate the depth of response because we believe the depth of response translates into long duration of response and anito-cel sees comparable depth of response to other BCMA CAR T products, namely 89.3% when measured at 10 to the minus 5 and patients were able to demonstrate this and were able to reach this depth of response within one month of dosing. The estimated six month PFS is 91.9% and the 12 month PFS rate is 79.3%. The estimated six month overall survival rate is 96.6% and the 12 month overall survival is 95.2%. In terms of toxicity, namely cytokine release syndrome, 85% of the patients experience grade one or less CRS including 15% of the patients who experience no CRS.
The median onset of CRS was four days, less lasting, and with the median duration of two days in the 85% of patients. As I said, the median onset was four days and 97% of patients either had no CRS or CRS that resolved within 10 days of anito-cel infusion. In terms of ICANS or neurotoxicity, 92% of the patients had no ICANS, so it was observed in 8% of the patients of any grade. All cases resolved and the median onset of ICANS was seven days and the median duration was four days. No delayed or non-ICANS neurotoxicity was observed, including no incident Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome at a median follow-up to 12.6 months. Similarly, none of these have been observed in the phase one study.
As I have alluded earlier, I have already mentioned, 92% of the patients did not have any ICANS and I think this slide highlights the safety and profile of anito-cel very much so. There were no cases of delayed neurotoxicity observed with anito-cel in the phase 2 study. Until this date, 150 patients have been treated with anito-cel. Between the phase 1 and iMMagine-1 studies, 38 patients have a minimum follow up of 25 months. No delayed or non-ICANS neurotoxicities have been observed and most importantly no secondary primary malignancies of T cell origin. No cases of immune effector cell enterocolitis have been reported so anito-cel has shown a differentiated safety profile in the phase 1 and iMMagine-1 studies to date.
In conclusion, anito-cel utilizes a novel synthetic compact stable D domain binder which allows for high transduction efficiency, CAR positivity, CAR density and T cell surface on the T cell surface and has a fast off rate. It has demonstrated deep and durable responses at a median follow up of 12.6 months. The overall response rate was 97% with the CR or better response seen in 68% per IMWG criteria. 93.3% of the MRD evaluable patients were MRD negative at 10 to the minus 5 and they were able to achieve that within one month of dosing. Median PFS and OS was not reached. The anito-cel safety profile is predictable and manageable. No delayed or non-significant neurotoxicities were observed, namely no Parkinsonism, no cranial nerve palsies and no Guillain-Barré syndrome.
No immune effector cell associated enterocolitis have been observed to date with anito-cel, which to me as a clinician is very important. 85% of the patients did not have any CRS or had a max grade 1 CRS and 92% of the patients did not have any ICANS. This is the ongoing anito-cel IMAGINE-3 study schema, which is a global phase C trial that is currently enrolling. Thank you for your time. I'd like to welcome Dr. Chris Heery to the stage.
We're going to come over here and conduct this panel. I'm going to start just with a little more context to some of the things you shared so that we can dive in on some of the questions that I think are relevant to clinicians. We get questions quite commonly to us as the management team and we say, well we talk with clinicians all the time and this is what they tell us. It's really important for people to hear it directly from you all. I'm going to just share a few of the points that do come up quite frequently and namely the last topic that you really touched on, Gurbakhash, was these delayed neurotoxicity events and enterocolitis events.
From the now multiple published real world studies, we see that the incidence of these delayed neurotoxicity events as well as cranial nerve palsies, putting that in that broad bucket, parkinsonism, cranial neuropalsy and then now seeing these immune enterocolitis events, we see them happening at a rate that seems quite high relative to other CAR T, particularly with Carvykti. The feedback we often hear is that has become a bit of a challenge. That is one of the topics I am going to ask you all about. The other topic I will want to ask about for you both to just think about right now is when you think about use of a particular product, do these events affect your conversation with your patients?
Does it affect the trade off, the risk, reward, consideration and then maybe weigh that for us between Carvykti and Abecma as the currently approved products? This is more data from the FAERS database, which, you know, I think really just complements what we just saw from the real world evidence data. I'll pause there and I'll ask maybe, Krina, could you start with the questions that I just listed for you?
Yeah.
No, I think it's an exciting time that we have these treatments for myeloma. I will say cell therapy is. I do research in cell therapy. That's my COI. But to, to really see these patients off treatment that we've never had in myeloma. That quality of life piece is so exciting. However, this is what we start talking about when we talk about consent for CAR T. Right now I have two options. I have cilta-cel and I have ide-cel. And when I'm talking about the different options, also therapies are not the same. So for my patients who are fit and I can do cilta-cel and not worry as much about these neurotox, I still talk about all the potential toxicities. And I think, you know, we talk about patients who get bridging therapy and they have less toxicity, which is great.
Unfortunately, even patients that have minimal disease going in, sometimes we'll see the colitis happen, sometimes I'll see the cranial nerve palsies. I think there's a distinction between what serious neurotox versus colitis versus not. It does take more therapies, it does take more management that those patients don't get that quality of life piece for as long as we would like if they get these side effects. I'll say the parkinsonianism and the colitis are the two big ones that I talk about with Cilta-cel. I don't really talk about with ide-cel because again, I have never seen it. With ide-cel, it's very rare. With Cilta-cel, not just myself, but my friends and colleagues around the country, we text each other about it to say, what do we do now? What have you tried?
Again, it is something that I talk about in terms of consent for CAR T. Sometimes my pickup patients will pick ide-cel for the safety profile, especially if they have standard risk disease. I think that risk balance, the risk benefit, is really important, putting in context of both the toxicity as well as the efficacy.
You want to take that one too?
Yes. You know, as Dr. Patel highlighted, we are very fortunate to have these therapies and they very much have a space even. CAR T is continuing to evolve. I think with each evolution of the product, we're getting safer products. We know that these products are efficacious, as highlighted by the success of their counterparts. Now we're sort of, you know, wanting to focus on CAR T's that not only just provide the safety, the efficacy, but also the safety in these. I would say my conversations over the one year has shifted greatly, actually. I would say especially in the last one year as there has been more data that has come out about these toxicities. The scary thing is we do not know how to manage these toxicities.
That's why we still think that there is a need for products that can offer similar efficacy and yet not put the patients at risk for them. We are also similarly texting each other, hey, how do we manage this? It's like winging it as we go along actually. Yes, it does play a role in my patient selection and how I counsel them. I would, you know, the T cell malignancies, that is now emerging as a possibility that also, you know, multiple myeloma patients in general get a lot of treatment. It's hard to tease out what is contributing eventually. That's a discussion that I also have as well
right now.
That's super helpful, I think along those lines, I'm very interested to hear how that's affected where you choose to start cell therapy. Obviously we've seen the approval of Carvykti in second line, Abecma in third line. Are you using cell therapy in second line commonly or if not, what are the, what's the limitations there?
I think we all have been enthusiastic as CAR T moved up and at the beginning I thought I would be using much more than I am doing right now. Especially because there are other regimens that can give you long term PFS such as the Dara, Kyprolis, Dex regimen. When that is available in the second line. Right now for me, I reserve CAR T in the second line mostly to patients who are functionally high risk. These are the folks who relapse within a year, year and a half, or even two years post auto transplant or first line therapy. People who are young and they have high risk cytogenetics or they have a very aggressive clinical relapse. I think that it is a small subsection of patients that I originally thought who would be going for CAR T.
Yeah, I agree.
I think we started with the high risk patients. Again, risk benefit ratio matters for if you have high risk or standard risk. If you're fit or frail. If this is early line or late line, I think the, you know, I'm excited about the possible plateau that we're seeing with Cilta-Cel. I mean, it's the first time we're seeing that again. I think it's potentially a class effect. If you have similar efficacy, but without that toxicity, that's really important. To have a third of patients. You know, the flip argument that my patients and some of my other colleagues have is that if you have a late line therapy that can put a third of patients into this great remission, that's where the risk benefit ratio for these toxicities are okay, versus you do it in second line.
These patients that end up at a younger age getting some of these toxicities that can cause problems. I mean, this is what we talk about. You know, do we have other options? Do we use those right now and then hope that we can, you know, get you to the CAR T down the road and you'll still do well? Maybe, you know, if you get the toxicity, then it's okay that at least we tried everything else before. Because if they get the toxicity in second line, that's devastating because I have all these other options that I can't now give. It's the opposite of what I was trying to do.
Right.
To that end, there's been a lot of discussion over the last eight months or so around risk mitigation strategies for some of these adverse events. Have you found or have you used any of those? Have you found any of them to change your thinking on how you counsel patients or influence your willingness to then move therapy to earlier lines as a result of thinking there is a mitigation? Or are you not quite comfortable that that's reality yet?
Yeah, those are great questions, I think. You know, I still bring. I'm a CAR T enthusiast, so I still bring up CAR T the second you're eligible for it. Because I need to know if my patient wants it or not, number one. If we're not going to go now, at least I know what to do to make sure I can do CAR T later. The second thing is everybody has different philosophies in life. There might be a patient that says, I really just don't want therapy. Give me the CAR T. If I go over everything, they still want it, we do it. I think the mitigation strategies are. I think it's important that we think about these things and try to. I think we don't really know right now.
It's, you know, I hope giving steroids or something if the ALC gets too high, which is what's happening. Maybe the ALC is a biomarker. I will say it's also a biomarker for response and efficacy, though. Which are the patients that still get the toxicity versus those who are just going to do well and get great efficacy? If I do a mitigation strategy, am I going to affect the PFS? We don't have that data. For us, we don't do the mitigation strategies as of right now. I wait till they have a symptom and then throw everything at it. You know, again, I, you know, we had a patient recently at ICANS got 4 mg of dex and they still have CAR T around. Thankfully, we got the ICANS treated. I'm not going to treat everybody with 400 mg of dex.
I think there's. These are biologics and T cells are not drugs. So everybody's a little bit different.
I think the most important risk mitigation strategy is I try to cyto reduce the patient as much as possible before I take them to CAR T. I think that pans out in terms that should be even classified, not just as a response to cilta-cel or ABECMA or even possibly anito-cel. We just know the cytoreduction and taking the patient to CAR T cell therapy in that setting where the disease is controlled is good on all fronts. I think the myeloma community has gotten a signal on that. Similarly, I think the verdict is still out. I do not know if this dexamethasone mitigation strategy is the solution. I know many people are doing it, but I think I have not adopted it fully for the right patient. If there is no.
Like I said, if everything is going bad, you're going to try everything that comes your way. At this point, I have not implemented it, but my colleagues have.
Either of you tried systemic or intrathecal cyclophosphamide for any of these cases?
For colitis. Again, I haven't had Parkinsonianism. We have been lucky, I think, but colitis, we gave the last two patients and my very first patient with colitis unfortunately passed away from horrible sepsis because everything we tried just made their immune system worse. My last two patients, we ended up giving 2 grams per meter squared or 1 gram per meter squared of cytoxin just to try to kill the CAR Ts and see if that helped after trying other local therapies, GI therapies, et cetera. So far, they're out of the hot ones, out of the hospital without diarrhea, but there are still some T cells left. We're watching very closely and kind of seeing as these numbers go up and the other patient is still in the hospital right now.
Okay. Yeah, I think enterocolitis is now giving us a lot of pause. I have myself not treated a patient. I have not seen someone with enterocolitis, but my colleague have and it's been a horrible case. Somebody who has been in the, who was in the hospital for almost nine months, couldn't manage the enterocolitis. That led to one episode of sepsis, to the second episode sepsis, the third episode of sepsis, to the patient getting their leg amputated eventually and now is mentally. They are in remission, but they're mentally devastated and are almost becoming narcotic dependent. You've seen this young person who would have, you know, maybe CAR T was really indicated in their setting because they were young and they had myeloma, which itself is a high risk marker, but it makes you rethink a lot of things.
I have not tried cyclophosphamide yet.
Okay. Maybe we can move away from that just a little bit and also talk about other therapeutic options. Krina, you mentioned this plateau that we're starting to see with CAR T. I think I've heard you say that it maybe puts myeloma into the category of lymphoma, which is really exciting, I guess. First question, you've both used anidocel. You've seen the data. Do you have any reason to believe that the sort of plateauing effect that we've seen with Carvykti couldn't be seen with a CAR T with a similar efficacy profile in terms of CR, MRD negativity, et cetera. Do you think that that might just be unique to Carvykti?
No, I'm excited to see the long term data. If I could fast forward to five years from now, I'm really happy. No, again, I'm hoping this is a class effect. I think it can be a class effect. We didn't see it with Abecma, but that's a different CAR T completely. I think the manufacturing and just the ability to get these patient cells, we're better and better at it. I think it's going to actually improve outcomes because again, when I know when I'm getting the cells, I can give the bridging that I need. Even on study, it's actually been easier to do it now, partly because we're smarter, but partly because it's just been a lot easier to get the cells and know when they're coming in and moving forward with it. The logistics matter in T cell therapy. Right.
They matter a lot actually to our teams for us to be successful.
Yeah, I think likewise. You know, I don't have any doubts that the efficacy will not hold. I think it's exciting, it'll be exciting to see how this data plays out. The safety profile to me is actually the most exciting part. I think, you know, the 17 day turnaround time that was highlighted on one of the slides as clinicians, when patients are getting through CAR T. CAR T is like a very, it's a high maintenance therapy. It requires an army of people to actually execute. There are a lot of folks on the nursing end, on the patient end that are constantly talking and coordinating.
To know when the product is going to come and you be the decider when you're going to give that therapy and you can plan that at least a week or two in advance, I think that's an accomplishment and that's a goal that we strive for. We have been striving for that for over the last four years actually. I think that's an advantage that's going to be leveraged when we may have to pick one product versus another. Right?
Yeah. I was going to say the studies that we have right now, you know, with Imagine 3, I could give all those patients cell to cell, but I talked to them about the both profiles for both products, the efficacy that we have so far. The majority of my patients who are willing to do a, you know, randomized study, pick that study. Right. Because they say, oh, if it could be safer and it's still really good, I want a chance of getting that CAR T. That's how I able to get patients on a randomized study even.
Okay. Yeah, yeah. Those points I think are really interesting and I maybe want to highlight what you were talking about with planning because what we hear a lot is from various institutions is that there are probably enough beds and there are probably enough staff to treat many more patients if the planning could be more cohesive. The moving parts actually make it so that you kind of have to be overstaffed at all times to account for the variability. Is that your experience as well? Do you have this, you know, sort of crunch that can happen as a result of moving timelines for when the cell therapy arrives and needing to change, bridging therapy, et cetera.
Me, that happens all the time. We're constantly having to, hey, the patient's going to come in one week on this date, plan for this and this, and then two days before, okay, we either don't have the cells or something's happened and we have to remove that. There might be a time when we have five or seven patients with the same product going in. We don't necessarily want that. Right. We want like a sort of a continuous flow of patients. Because more volume means being able to pay less attention to those patients actually naturally. Yes, I do. We do see that. Yeah.
No, I think my team, if my team's happy, I'm happy. If my team's not happy, I threaten to quit as well. We do actually hire a lot more people because it, the logistics just take a lot. I think, you know, the Kite connect that you were talking about, I can't tell you. Since the day myeloma got CAR parties, my coordinating team that deals with all that, they hate every other one. They're like, why is this like this? Because this one's so easy. It makes so much sense. Why do I have to deal with all of this? That is where all the communication happens. If my team can't do it, or they put it to the side because this one's easier, you know that affects our patients and being able to bring them in on time.
I think that out of spec rate too, that's where, you know, yes, most of the time I get my cells in four to six weeks, but when there is a patient out of spec, we don't figure that out till later. You have to actually talk to the team again to say, please do more bridging, figure out, you know, if they're responding or not. It just makes it a little bit harder to get those patients back and in pristine condition that we want them in to give them the cells.
With the out of spec, actually it creates a lot more work. Each institution sort of does it differently. We have like protocols. The patients essentially end up into a study protocol, which itself is, it requires maintenance and resources on the academic sites. Right. Yeah, not something that we want to deal with all the time.
Do you compare notes with your lymphoma colleagues and say, that sounds so much easier or what is that experience like? Compare, you know, comparing and contrasting the myeloma department versus lymphoma department. Have they seen, you know, because of the availability of multiple products that are delivered with a lot of consistency. You know, obviously Kite having been the leader in all of that for a long time now, is that a different experience within the institution?
You know, in my experience, I feel like when, because maybe lymphoma had been there before myeloma got CAR T, they had kind of eased up the kinks of it. It always seemed like it was a more seamless transition to get someone getting CAR T. We are going to plan this out. Whereas in myeloma I feel like we have always been trying to, but that is the farther deal with it. I think up until now, actually that has been the story that it is always like, oh, we could do this, we could do that, we could. The planning is sort of like very haphazard. It is not as smooth as I have seen in my lymphoma, actually.
Yeah, no. My team will say again and again, they're like, why can't everyone be like Kite again? This was before I even started working with any of you and that you guys even joined Kite. That was the gold standard for my entire team, that why can't everybody else be like them?
Yeah, I mean, I think departmentally you fall within the same group as lymphoma.
We share resources. It's the same people that work and they know everybody and they rank, they know what its rankings. Myeloma is usually at the bottom.
Yeah, that's funny.
Yeah, great. Also on the topic of compariting, you know, how you're thinking about what you're going to use for treatment for patients. Obviously we've seen a real improvement in the T cell engager therapeutics over the years. I mean, it's, I'll admit, better than when I first saw a T cell engager therapy in I think 2012 at ASCO. I thought, wow, that's, you know, that might be the best it'll ever be. Things have improved really significantly.
The observation though of the plateau effect in CARTITUDE-1 seems to have brought up for a lot of people this question of, if I give a T cell engager before a CAR T, am I giving up a possibility of long-term durable benefit with high quality of life in exchange for something that I guess is a little easier in some cases to deliver? Do you, I mean, can you just comment on the conversation maybe you've had with your colleagues on that topic? I know it's recent, but over the last month or so.
You know, if you ask the folks who are at the IMWG conference and who treat myeloma, CAR T is always preferable if it can be delivered to the patient and the patient and the candidates. That's usually a number one go to. I think that's across the board. Certain patients are truly not CAR T eligible, whether they're frail or that. I think you exclude that patient population. I think myeloma keeps on surprising you. Actually just when we were having conversations. Oh, T cell engagers are going to move up but with them comes repeated toxicity of infections. Oral and skin toxicity that has not been well mastered yet. You have this treatment free interval, this phrase and patients want freedom from the clinic and they want time toxicity that adds on.
I think yes, the T cell engagers have come a long way and they are very effective and they will still be given in the myeloma space. I think the preference amongst us is still to go for CAR T because it leads to improved quality of life for patients. That's how I've seen this.
There's no randomized trials of course, but median PFS for the current CAR Ts is still much better cell to cell. Still way better than any of the bispecifics single agent. I, you know, I think the question of CAR T before or bispecifics getting it and then going to CAR T, we know that the, not just the response rate but the PFS drops so low that it's not worth it, it's not worth to get six months PFS if you're going to get a CAR T. In the end for my patients I tell them, you know, I think bispecifics after CAR T make total sense that if you're not in that 33% or hopefully higher for earlier line to stay in remission and we need to treat again.
Bispecifics at that point make much better sense because your T cells are back to normal, you're doing great, you're in better shape if not on continuous therapy with these side effects or serious infections that PFS 1 and 2, if we need that PFS 2 is going to be much better. Yes, I've had multiple conversations with local doctors recently because there's a few that are trying to buy specifics. A lot of my colleagues can't because it still causes CRS and it still causes weird infections and they need a hospital, but it's easy to get it off the shelf. When you're done with it and they're relapsing now, you've run out of things. Whereas the other way around, you actually have. If you get five years or even four years, let's say you have all these other therapies we've gotten in myeloma, then.
Right.
That they live longer because they have access to other drugs again.
I think some folks actually go to bispecifics because the CRS and ICANS seen with bispecifics is much lower. If you can offer them a CAR T that's 15% experiencing no CRS and the remaining that do, it's usually grade one or two, which is what we actually see with bispecifics. It makes the CAR T even more appealing, actually, that the immediate toxicity that patients dread, or even our community oncologists, who may be referring to us, dread. With only 8% ICANS, I think when there is an improvement in that safety profile and it's comparable to the bispecifics, you're going to have more of an appeal for CAR T.
All right.
Now we can play Predict the future a little bit. You both touched on a few really key points that I think I know. You both think everyone knows, but I do not know that everyone does know. The data that were presented at ASCO, looking at the subgroup of patients in CARTITUDE-1 who had a greater than 25% reduction in their disease burden with bridging, had significantly improved outcomes compared to the rest of the population. That seems consistent with what we have learned in lymphoma. It seems consistent with other clinical trial data and real world data. I would love for you to just talk about how you think about that in the real world. Different even than what we are allowed to do in clinical trials. Where you think that is going.
Sure, yeah. I think I was at a meeting earlier today. We think about CAR T as consolidation more. More than as a therapy of its own. Right. So I have a patient coming to me, let's say, you know, third, fourth line, wherever they are, they're relapsing. The second I see that biochemical progression, I start talking about CAR T therapy and we start getting financial clearance. Even if they're not eligible yet, we start working on everything, because the second they are eligible, I get their slot. I then start bridging and our plan is that in four weeks, five weeks, we'll go to bridging, you know, the CAR T.
If they're not responding, usually within two or three weeks, I check their myeloma labs and if it looks like they're not responding, I actually switch their bridging and we change it to something else until they have a response and then we go to CAR T. We might delay actually giving LDC or the CAR Ts until we know they're coming down because it is such a big biomarker for toxicity reduction, but also efficacy. I think the other thing is when people are coming in with horrible relapse. My high risk patients, they might not just biochemically progress. They're fine one month, the next month, all of a sudden they have all this disease. I can actually start treatment. I can start Dara-Pom-Dex, Dara-KRD, and then as soon as I know that they're responding, then go to CAR T.
Again, these are therapies that don't affect the T cell. I'm okay doing it before apheresis and then I go to the bridging to even get further reduction and then to CAR T. Remember in CARTITUDE-4 there's all these patients that never got SOC cells. That's because we have to have a two week washout. You can't have any therapy that gives you a response before you go onto the study. In the real world that's not the issue. We don't have to do any of that. Most of my patients get their cells now because of that.
Yeah, I agree.
Same.
Yeah.
Let's maybe add on to that then because most of the CAR T trials to date have not incorporated every therapeutic option for bridging because it either wasn't approved yet or because it seemed, you know, maybe too risky at the time. Are there any of those therapy, for instance, bispecifics that you might use in bridging at this point?
Yes, I actually just used it last week. I had a patient who was getting, you know, who had gotten Aphrodis at a clinical, very clinical, relapsed with extramedullary disease and was not responding. I actually ended up giving talquetamab as the bridging therapy. Markers went down. Cells are ready, I'm ready to infuse. I like that profile going into CAR T because I just know that I'm not going to deal with the crazy CRS and ICANS and the immediate toxicity. I don't know what that means, you know, long term. I know there's been a whole discussion about, you know, disease control and whether that really, truly has an effect on those delayed toxicities. Yes, we are using bispecifics. Usually we choose a different target. The preference is to use talquetamab, not necessarily teclistamab or Elranatamab because they're both BCMA.
You know, we have that as an option now, which was not available four years ago.
Yeah, same thing. We know that before we did this, the question was if you have bispecifics around, will it make the CAR T worse? Like will it make CRS and ICANS worse? We have a huge series retrospectively, but that shows that it's actually really safe. It's late line. It's been amazing.
Yeah. One of our, sometimes our hesitation in actually even going to bispecifics is the T cell hit. Who knows, maybe another ADC will come around. If someone just needs a little bit of that, which does not really exhaust the immune system, maybe that is going to be an option. I do not know. You know, it is time to be seen. Yeah, you have more raging options than before.
You used a word to kind of close out our panel. You used a word that I think is associated with first line therapy, which is consolidation. That leads me to wonder then, are you in the camp that is thinking ultimately there's no better use case than use my best consolidation therapy when I have my best therapy to cyto reduce? Is that, are you in that camp that you're hoping to see CAR T get to that place because you think it's an ideal fit for that setting or are you still on the fence?
Yeah, no, I think it's about toxicity. I think efficacy wise for sure. I mean we see better MRD negativity than we did in transplant, definitely in earlier and later lines. I do think that CART-6 is going to win for efficacy. It's the toxicity we're all looking for. Right. That melphalan, high-dose melphalan has been around a lot. You don't have mortality. You know, it's less than 1%, 0% CIB, MTR. It really comes down to the tox. If you have another product that's going to do something similar and not have toxicity, I would put all my, I would bet my money on it. I think it's different than high-dose chemo. Right. Again, transplant is chemo. It's not cells. Even though we talk about as consolidation, this is just a very different, you know, ball game.
I'm hoping that we're giving, let's say, talc Dara, you know, mezzi as an induction followed by CAR T. And then you do maintenance for a little while and you're done. In high risk patients, maybe you keep maintenance going, but standard risk, you get to stop everything.
Yeah. That is, I think, a future that we all hope for. Right? I mean, I think you said to me earlier today that we really even up until this year, no one's talked about very seriously about cures in myeloma. In other diseases, other cancers, cure has always required a multimodality approach, especially with, if you'll consider it, systemic or metastatic disease. In the rare cases of solid tumors that can be cured, those require multiple different drugs, multiple different mechanisms of action. I am encouraged by the excitement I hear from physicians like you about the patients you're taking care of and that there may be ways to optimize further with the right product at the right moment.
You know, I think we are proud to have worked with you all on this study, but also that this could lead to patients just not needing to be treated forever, which is a really exciting potential. On that optimistic note, we will switch over to our Q and A and I'll invite Rami and Michelle up to the stage if you all don't mind sticking around with us because some of the questions may be addressed to you.
All right. Are we on?
Perfect.
All right, thank you guys for a great panel discussion and for being here this evening. We will maybe start in the room. Like I said, extra credit for those who made it. Milan. And it looks like John has the microphone, so.
Great. Thanks, everybody. John Newman from Canaccord. Thank you to the physicians as well as to Arcellx.
You know, I think, Dr. Kaur.
You mentioned something that I actually had heard from another group at ASCO about pulling talquetamab forward and using it as bridging. My question is, when you have some of the CAR Ts that require a very long manufacturing time, does that require you to pull therapies forward into bridging and ultimately use them longer than you normally would such that maybe later on there may be not quite as attractive? I'm just curious about how you think about that.
I think you're asking more about whether the usage of talquetamab has bridging, right. I think even if, and how does that play into manufacturing? Did I get the gist of the question right? You know, as of right now, we want to bridge people and go into CAR T with the least amount of disease. Sometimes with our conventional therapies that we have, that's not achievable. Then we do move forward with talquetamab, usually. It's always good to know, it's always good to have a product ready before you're done with bridging, so you can plan. Even if that cycle of bridging is going to go, let's say your cells are ready, but then your bridging is going to finish two weeks later, that's okay.
Because the cells being ready and you being able to plan around that, I think is the most important option. I do not think if you use talquetamab as bridging, that means you cannot use talquetamab later on. I do not know if that was part of your question. Yeah, I would say, you know, talc exposure does not necessarily mean talc resistance, and it just depends on how long you use it for. Right. Most of us are using it for a cycle or two. Sometimes a cycle is more than sufficient. You make, and cycle just equals about 28 days. 28, 30 days. We may go into cycle two. You know, let's say the patient's kind of worn and torn out from all the hospitalization. You may want to just allow for them to recover, get stronger so you're able to bring them in.
Actually just allows for them to get stronger and better planning.
We would like to do the minimal amount of bridging if needed. If they're already responding, I only do the step-up dosing for talc because, you know, again, we don't see the toxicity. The longer they're on it, the dysgeusia, the other issues going into CAR T, and it lasts for a little while, so it's not just one month and it's gone. You don't want those quality of life issues. If we can minimize it and we have the cells ready, but they've already had a response, I'll stop in.
The middle of the cycle and go,
yeah, I agree.
Great.
Daina, microphones. Can I hear?
Hi, Daina Graybosch from Leerink Partners.
Thanks for doing this.
I thought the survey you put out.
The beginning, the one number that really.
Jumped out was the difference in the.
Community's response from 2024 to 2025 in their willingness to give CAR T share in second line.
I wonder if the doctors—I think it went from 26% to 11%. I wonder if the doctors could talk about what you think is specifically driving that actually big increase in pessimism or more pessimistic. There it is. Whereas the academic, the treaters got a little more optimistic on their use.
I can take it.
Okay.
I think for us, we know what CAR T means in the grand scheme of things. For us, it is like, okay, we have something that especially our high risk patients. In the academic side, I will see a lot more younger patients with high risk disease. I think in the community, you know, again, a lot of other therapies are out there, bispecifics. They have DARA combinations or ESA combinations that they can use. It is hard getting community doctors to send us patients, especially if they think that a treatment is too high maintenance or the toxicity is bad. They will say, we do not want to give it second line. We think it should be third or fourth line.
What we've always told everybody is that once the CAR T, if you're one line of, you know, we want to see them one line prior to CAR T because again, community versus academics, you know, they think we're going to steal their patients, all these things. We try to make it that we're not trying to steal your patients. We're here to help you when you need us. When it went to second line, that means they would have to send us at first line. Again, I've done a lot of talks to community doctors to do education. What I hear all the time is, you know, the toxicity sounds pretty bad. I don't want secondary malignancies. This weird neurotox. My patients are older, you know, I don't really think that they want to get this done.
We'll just sort of, you know, do these other things that, you know, here at the local hospital. I don't know if that's.
No, I think that's exactly that. There was definitely a lot of enthusiasm. I think because the toxicity is probably what's preventing that, it is probably driving that number going down, actually. I agree with Dr. Patel that we like to see the patients one line prior before we actually have to give them GARDI so we can start the logistics and planning.
Maybe it's important to point out that the nuance in this slide though, Daina, where the difference that you're talking about is specifically focused on the currently available CAR T therapies, not assuming the availability of anito-cel where that actually looks quite strong again. I think that does support the idea that this is mainly driven by toxicity or challenges that exist with the current therapeutic options.
Yeah, I said that earlier. I think it is important, as Chris mentioned, that the in-market experience seems to us to be impacting this variability with the current CAR T's whereas the future state seems to be fairly consistent. Again, these are very large quantitative, kind of statistically powered studies and I found them to be very reliable in the past. So we do trust this when we see it.
One more.
Sure.
You talked. It was really nice to hear the.
Cases about how you're bridging today in the real world.
I wonder if you could talk.
About the real world versus the protocol in Imagine 3. Thanks.
Let me just lay the groundwork for Imagine 3 just because that's public information, but I want to make sure everyone knows where we started from. Imagine 3 randomized trial, obviously, and patients have to have a selection at the time of enrollment for what their standard of care would be if they're assigned to the standard of care arm. If they are assigned to the anito-cel arm, that's the therapeutic option they have to use for bridging. That is just the groundwork for Imagine 3. Please take it from there.
Yeah. I think having it earlier line makes it a little bit easier that, you know, we have these washouts. I will say the washouts are the bane of my existence for all CAR T protocols, but I have a lot of late line, even post BCMA CAR T protocols where that is a lot harder to deal with than earlier line. It does make it more difficult compared to standard of care where I can do what I need to do to get that patient through. Right now, yes, we pick the standard of care based on I pretend my patient's getting anito-cel and I want them to get the best bridging. I pick the standard of care based on that.
Right.
Hopefully that's the therapy that's going to actually work for bridging. If they get it as standard of care, that's the best potential option for them too. The washouts will for any trial just make it a little bit harder. It's the same, I think, right. Two weeks.
Yeah.
Maybe, maybe just to drive home that point, if you just look at the data with KDD, for instance, in the clinical trial that led to the approval of KDD, the response rate isn't 100%. Even though you're going to pick the best regimen for the patient, there is still a chance they're not going to respond to whether it's the control arm or whether it's the bridging in Imagine 3, that's still a distinct possibility. The challenge that I think Dr. Patel is highlighting here is that you don't have another option in a trial like that. That's just not allowed. That isn't a limitation you'll necessarily or definitively will not see when it's an approved product, whatever the product might be. The clinical trial design doesn't influence what you can do for bridging.
Yeah. That's in the real world, when you're doing it, it's your own discretion and what you think is going to work, what's available to the patient and how quickly you can get it.
Yeah. For instance, we just heard cases of using talquetamab as bridging, which obviously did not happen in any of the CARTITUDE studies.
Yeah.
Krina.
Hi, this is Krina from Arcellx. I had a question on the long term follow up for Cartitude 1, which was presented at ASCO and EHA, which showed that patients with lower tumor burden ended up being long term responders with anito-cel. Probably it's going to have 17 day turnaround time. How are you thinking about debulking the tumor with bispecifics?
Potentially, yeah. Less tumor burden?
Yes. I mean, honestly, I know we encourage bridging therapy, but if somebody, the goal is you get the patient earlier where the disease is not as aggressive. You're not dealing with M spike monoclonal protein. That's a disease burden of 5 grams. You're dealing with that 1 gram or 2 grams. So you actually don't need bridging therapy. That would be ideal for me. Do I get that in real life? That does not happen. I usually. I think I lost track of your question. I'm sorry.
Yeah, sorry. Go ahead.
Now, I was just going to say. If I have 17 days and a patient needs bridging, I can just do the step up dosing which takes one a week and you actually see a response. I've had a few patients that had allo transplants before or renal failure where I did not want to give them too much because I was worried that it would put them into toxicity from the talquetamab itself. I just did the step up dosing and then a week later they're ready to go. If I had cells ready, I can do that. Especially with bispecifics. I think it's harder with other therapies that are actually available in the study, for instance, that you can't do that.
At least having the cells ready, I know that I can go as soon as I need it, but I think I'm excited for the real world part of this.
Let me just highlight, because Daina was asking the same question. I just want to make sure we're clear on this. If you give bridging therapy, for instance, in Imagine 3, there's a washout window from whenever the last dose of that therapy is to when you're allowed to give the cells. In the real world, you don't have to wait. What it means is that, for instance, you could bridge a patient, have the cell sitting and waiting in the freezer for a week or more because they already arrived, because they turned around in 17 days. That is pretty unheard of at this point in myeloma. It's a good problem to have because it gives the physician the flexibility to make the right decision for the patient.
We actually want that problem. We want the cells to be ready. Then it's at our discretion on when we want to give it. Unlike the other way around where we keep on giving bridging therapy, but we don't know when the product is going to arrive. We are actually more predicting and not necessarily planning.
Our experience in Imagine 3, which we've shared before, thanks to how incredible Kite is at manufacturing, is that cells are generally arriving before the patients are done with bridging. It is almost like in effect an off the shelf therapy. I think both physicians have spoken about the predictability and the scale with which I think one of the things that's really underappreciated here is to really, truly address second line, you have to be largely scalable and predictable. Otherwise it's all theoretical. To really, truly address the number of patients that are needed here, you have to be able to do it the way Kite is able to deliver.
Other than that, without getting this to that less than 17 days, without getting the inspector rate, without having the Kite connect and the logistics and then the reliability, kind of the wheels fall off the bus. I think that's something that isn't really fully appreciated. I don't know if either of you want to add to that.
Yeah, I'm just going to add in reference to your question, you know, the real-life case, my patient got bridging, got talquetamab, had a response, finished step of dosing, and my nurse is asking, when do you want to give her the dose again? I said, hey, she'll be due for the next dose in two weeks. Let's plan for that. I do not know when the cells are going to be ready. I cannot make a decision today on when that patient will get their cells. What I'm doing is I'm on the edge, keeping a check on their markers, and the cells were supposed to be ready this week. I have not gotten a word that the cells are ready. I'm going to have to end up dosing for that, start of that the next week, the dose next week.
That's a situation we do not want to have. We want to be in the other situation.
Thank you.
Maybe while we're transitioning, I can just point out, though, that this debulking idea, consolidation idea also may allow for more predictable outpatient dosing if you know which patients are now debulked.
This.
Is that a fair assessment or have you had a different experience?
Yeah, the less tumor you have, the less CRS and ICANS, and the more I can keep people outpatient. We know that bridging helps with decreasing toxicity short term and long term.
Yes, I agree.
All right. Now we have some online questions that I'll read out loud. This one's from Jason Gerberry at Bank of America. What line of therapy are you mainly prescribing Carvykti, and I'll add in Abecma, too. How do you see the supply of CAR T naive patients in fourth line and fifth line when anito-cel is commercially available?
Currently, I have a very small subset of patients who are getting second line CAR T. Those are my harvest patients with functionally high risk relapse earlier within a year or two of stem cell transplant. Majority of the time, it's being given in the third and the fourth line setting in my practice.
Yeah, same. I think there are quite a few patients out there that are third line already for other things. I still get those patients. We talk about CAR T and I give it to them. I try to go at third line for most of my patients. Again, because of the fact that I need better bridging. I need predictability, and that is going to happen in earlier line for the current products. Again, I will take every patient that comes to me for CAR T too.
CAR T.
There was a second part to that question, right. How do you expect the supply to be if you've given patients CAR T in third line? What's going to that look like for fourth line? I actually think the conversation is changing as patients are more informed. That's going to be part of our counseling, right. If there's a product that has similar efficacy and less of that toxicity, the enterocolitis and less risk of that toxicity, enterocolitis and parkinsonian, that patient is going to be willing to wait to get the CAR T in the fourth line space versus before. I've actually, you know, one of my patients said, Dr. Kaur, I'm not the one who wants to try out the first model of anything. I want to wait it out.
I want to see when others have done the test driving and then I can go on and the second one. There are patients like that. I think that highlights that there will be. There will definitely be a supply of those patients.
All right, and this question is from Tyler Van Buren from Cowen. As a patient or as the patient preference to enroll in the ongoing second line plus IMN-3 trial as opposed to the commercial Carvykti as opposed to commercial Carvykti, given the lack of delayed neurotox and parkinsonism was mentioned, what do you expect peak penetration of Carvykti to be in second line? And how much could that increase.
With.
A lack of delayed neurotoxicity as has been observed with anito-cel?
I think this five year update, right, for Cilta-cel, I do think people are like, oh my gosh, CAR T again, it's changing the way we think about myeloma, which is huge, huge because no one's ever thought that we would have a therapy you give once and then you don't get any treatment for five years, especially in relapse refractory. I do think I have a few more patients that are asking about CAR T that might not have before. It's brought great attention to CAR T. Again, coming back to the toxicity, if I have a standard risk patient, so my high risk patients, I'm going to take them as soon as I can. You know, that's something that I need to do. These are patients that don't get to third or fourth line and I can get them to CAR T.
They're the ones that fall off. For standard risk patients, again, you talk about all the potential options. I think about, will I have bridging available? I think I will because we have all these new therapies. Now it's up to the patient and us to say, what's the right move? A lot of my patients in the past have picked Abecma because they thought it was safer. If you give better bridging and you can give a CAR T and get better outcomes and maybe I have less toxicity. I think, again, there's going to be some patients that go in second line and third line, even if they're standard risk. A lot of patients will say wait, or a lot of physicians will say, I'm going to give my things first, and then we'll do CAR T after.
Yeah. If the patient goes on trial for IMAGINE-3, they still get standard of care therapy. I think IMAGINE-3 has some of the best standard of care therapy options that are available to patients. If they progress on that, they can always move forward to Carvykti. Carvykti will always remain an option for them. You know, two years ago, when I thought about any trial that was evaluating patients in the one to three lines of therapy and we knew Carvykti was going to be approved, there was a little bit of nervousness, like, oh, my God, CAR T is going to be available. How am I going to get a patient onto this study? I actually think that is no longer true. That was. That was.
That was a fear that really had no basis because there are plenty of patients who do not want to take on that risk and will wait.
At this point, what is the probability of a delayed neurotoxicity event or Parkinsonism case showing up with anito-cel treatment? Have you monitored for ALC in the anito-cel trials to inform treatment? Have you excluded patients with peripheral neuropathy with Velcade?
There's a lot in there.
Yeah.
You want to take the psychology?
I can take all of it. Yeah. We didn't exclude patients with peripheral neuropathy because you couldn't enroll a trial if you did that. We didn't monitor ALC for how to intervene on anything. We obviously monitored CRS symptoms and intervened if patients had CRS, particularly CRS that needed ongoing intervention. For instance, a patient had recurrent fever, rising inflammatory markers, et cetera. I think, as we've shared before, of the patients who got any dexamethasone, 60% of them only got a single dose of dexamethasone. There was no prophylactic dosing of dexamethasone. This is really just a difference between products and I think any other comparison between them really falls short because these aren't the types of interventions that would preclude. As we just heard, ALCs continue to rise even when you give 400 milligrams of dexamethasone.
I think that's pretty well documented at this point. We've seen it in the ZUMA-1 trial, for instance, that you could give steroids at different times and doses. It doesn't affect peak CAR T expansion or area under the curve.
Yeah. Just to add that, build a little bit on what Chris said. These are fundamentally different therapies. I feel like a little bit of this dialogue is pretending like we're using the same binders and one therapy has this issue and it's like a mystery why the other one doesn't. It is very clear the only difference between the two CAR T's is that one has one binder and the other one has another. Fundamentally they are different. As to the question of probability, I have to channel my professor in probability and stochastic processes. Dr. Yates is very memorable, one of the better professors I've had. I think if you plug the difference of these observed rates between cilta-cel and ide-cel, you're going to get a P value with a lot of zeros in it. Like statistically they're very, very different.
We cannot sit here and tell you that we can never have a case. The more interesting question is, does it matter? I will ask the physicians, do you think about Parkinsonism when utilizing Abecma? Headshake.
No, no.
Investors do not think about parkinsonisms or delayed neurotoxicities when it comes to Abecma. Abecma has had more than one case. They have had multiple cases. The reality is that at some low level of cases inevitably happens, it seems for attribution or other reasons. We have had sufficient follow up with a sufficient number of patients to know that this therapy is fundamentally different from any other therapy out there in the myeloma space. We are very confident in that profile. As I shared before in closing on this particular point, when you go back to the CARTITUDE-1 data from five years ago in ASH 2020 with similar median follow up as we have now, the profile of Carvykti has not really changed from an efficacy, safety, manufacture ability.
We believe that we have a similar degree while we do in fact have a similar degree of follow up with this therapy. As a result, we're quite confident that on a go forward basis, this is the profile of anito-cel. I think for some people, like, there's this hypothetical of like, what happens if you get a case. I can kind of understand a little bit more if ABECMA didn't exist. It does exist and we know what happens when they've had a low level number of cases. The answer is absolutely nothing. We're talking about a materially different rate here that Chris went through earlier and materially different expenses as both Dr. Patel and Dr. Kaur shared earlier. That is a different world than the world of anito-cel.
There was a question about peripheral neuropathy. Almost all patients with myeloma have peripheral neuropathy. We end up not excluding them from clinical trial. We almost end up never excluding them from getting Carvykti even. That's just the reality of the patients we deal with. I don't think that is a barrier to us being able to give them any CAR T cell therapy.
Can you imagine a clinical trial in myeloma that excluded peripheral neuropathy? Honestly, would it enroll?
No, it would not. Even if we knew there was grade one, that would not be written in the chart. If that was exclusionary criteria, the therapy was really effective.
All right, and.
Are.
Are you able to provide insight or. Sorry, this one's from Judah Frommer from Morgan Stanley. Are you able to provide insight into prescriber affinity for anito-cel as broken down by the product's clinical data profile versus supply and manufacturing benefits that are born out of the Kite collaboration. We're curious as to whether the Kite relationship and related superior manufacturing is a driving factor for certain docs.
I think both. Right. The efficacy and lack of toxicity. Efficacy is always going to be number one. I will go through painful things if I have to for my patients. If something is superiorly better, but if they are similar and one has better toxicity, well, that is the next reason. The icing on the cake is the fact that I know when I am going to get the cells. My team is happy. I am happy. I am not burning out, just trying to get CAR Ts to my patients. That is sort of the secondary. Again, really important. It is still secondary compared to the efficacy, but exciting. Again, my team is excited that Kite might be the people we use for everything rather than just lymphoma right now.
All right.
And.
For the management team, can you talk about your commercial? I'm sorry, this one's from Qize Ding from Redburn Atlantic. One question for the management team. Can you talk about your commercial launch plan for anito-cel in community hospitals and the major hurdles?
Yeah, sure. Look, we're obviously, as we talked about, really excited to cover the entirety of this market again jointly with our partners at Kite. We do believe that the community element here is going to be really important. It's a big part of why we shared this deep level of detail on the research because we are really encouraged by the reaction of the community physicians to the anito-cel profile. Getting into a little bit more detail, which I covered at a high level, we will be co-commercializing with Kite, meaning that we will also have a sales force. Between the two of us, we will very much cover the entirety of the market, including the community.
We have very detailed plans on how we will do that because we do believe it is critical, again, for our goal is we really, truly believe, and you heard that today, that we have the best therapy for these patients that God forbid, if we knew anyone personally that needed a myeloma CAR T we would want them to have this one. We are going after this market with that vigor to make sure that every single patient who can benefit can get there. A huge part of that is the community. I do not know that I can give you a lot more detail without showing a lot more detailed plans, but I think this is one of those where you have to trust us. That is a huge focus of the launch from almost day one.
Because we have this dual salesforce, we feel like we'll have the coverage to do it and we will do it.
If I could add one other thing on, the other element of this, of course, is education with community doctors. They are usually covering many, many diseases and many different kinds of patients. Part of our role and responsibility as a company involved in this space is actually to help share the knowledge that you heard from these physicians with physicians who are taking care of lots of other diseases. That is not always easy. Part of what our job is is to create data packages that will allow us to be able to go and share that with community doctors and demonstrate to them that this is a therapy that you cannot forego because you are giving up too much.
We believe that, obviously, but it is part of what we will do in the launch of anito-cel is help to share that message more broadly, not just with the doctors who give the therapy. They're already fairly convinced, but with the doctors who have to refer the patients for this therapy.
All right, and the last questions are from Gil Blum from Needham. Do you understand or do you consider anito-cel as potentially expanding the market with difficult or frail patients? And for delayed neurotoxicity, what in your view is sufficient follow up to exclude as treatment associated?
I guess it depends on your definition of failed. But yes, I think there is a, you know, when we think of Carvykti, we give it to the younger fit patients. That's the number one age group. But, you know, I would say mid-70s, we get worried a little bit about giving Carvy, and we start thinking about Abecma as we go into the 80s. I definitely think that that population that's not going to be as physically fit will be actually opened up to anito-cel more so than even Abecma. And it'll take a share of the piece from even the Carvykti patient population. So yes, it will, I believe. Yeah.
I don't have anybody above the age of 78 with Cilta-Cel. The majority are 65 or younger. We have multiple patients in their 80s and even a 90 year old with Abecma. Again, with the safety profile here, I'm not worried about the neurotox. That's really the main issue, the delayed neurotoxin. These patients don't have the, you know, the reserve to actually go through all that steroids and Cytoxan and other treatments when they're already going through CAR-T. That's the reason I don't do Cilta-Cel. If I don't have that, then I wouldn't be afraid to try Anito-cel for those frail patients. Even though I know on trials none of those patients are ever on any of our studies. It takes the real world to figure it out.
I would not be afraid to use it as we are as a group. I think with cil right now for patients going into seventy-five, it sounds like.
Particularly if you could debulk the patient in your optimal way.
Yeah, I think I would add from an Arcellx perspective that we clearly believe and supported by this research that anito-cel is going to expand the market broadly and it's going to expand in a lot of different ways. It may expand it by allowing use in some older, frailer patients. I think one of the biggest takeaways, hopefully here it's going to expand it a lot in earlier lines and second line, you're hearing a continued hesitation of utilizing CAR T due to toxicities and in earlier lines it's going to expand it by driving into the community. The profile is clearly much more favorable in a community setting. To be able to even access these patients anito-cel is going to play a significant role.
From our view, again based on our experience, what we've heard from physicians more broadly and then specifically from this research, that it's going to be significantly expensive. As to the other part of the question, what is the sufficient follow up needed to assess whether or not this is related? I think I can say from what we know of Carvycte and I'd love to hear from you in closing that it seems like these events tend to happen in the first one to two months. We had a minimum follow up of four months with imagine on 117 patients plus the phase one which obviously had significantly longer follow up. We're quite confident in the profile again. Maybe in closing, love to hear from the two of you.
Yeah, I think it's the delayed neurotoxicities. They're delayed but they're after day 30. So even our cranial nerve palsies happen in that third to fourth week. For the most part we have seen it up to the second or third month but after that I don't expect. If you don't have any neurotox after that third month, I don't expect any of my patients to have issues after.
Yeah, I think when you have even though the number in your phase I, what is reassuring to me is the N is small but you have almost a 38.1 median follow-up. Right. If there was a signal, say not Parkinsonism, we should have seen it by now. And the patient population probably early on in your trials was sicker than later on and we often tend to associate those two. I think there are less chances of seeing these types of neurotox with anito-cel. I firmly believe that. Not because I'm over here. I really do actually.
Thank you both for joining us and for sharing your wisdom and insights. Hopefully we make I made Dr. Yates proud today some of that recall of statistics. Thank you all for joining us here and via the webcast. We continue to really appreciate your time and your interest in Arcellx. Until we meet again at the next meeting. Thank you.