There are experience. Yeah. Yeah. Sure.
Okay. I think we'll get started. Hi, everyone. My name's Daina Graybosch. I'm a senior analyst here at Leerink Partners, covering largely immuno-oncology and also Gilead, which is broader than immuno-oncology. Today I have the pleasure of talking about cancer with Cindy, who's the head of Kite. Thank you for joining us.
Thank you for the invite.
I appreciate the time.
No, thank you.
We are going to jump right in. I'll also leave maybe about five minutes at the end if anybody in the audience has questions. Let's start with your BCMA CAR-T, which Kite has partnered with Arcellx on. I think there are multiple potentially differentiating attributes for anito-cel at the BCMA CAR-T. I wonder which of those you think is going to be most impactful for commercialization as you look forward to a launch next year.
Yeah. As a reminder, the data looks really compelling. We've got a 62% complete response rate, which we know is going to deepen over time. We have a 97% overall response rate. What we're seeing from an efficacy standpoint, both in the high-risk population as well as, I'll call it, the general population with myeloma, looks very similar. High risk doesn't seem to have an impact on the efficacy. From a safety perspective, we do see differentiation as it relates to we have for grade one and I guess no CRS events were at 86%. A majority of the patients at most get a fever. We're also seeing differentiation on the long-term neurotoxicities where we have a low rate of ICANS and we haven't observed any of the long-term neurotoxicity.
I think that overall the safety and efficacy profile we're really excited about commercially and think that that's going to make a difference. If you pair that with the relationship between Arcellx and Kite, we have brought in our global manufacturing excellence. We're bringing the vector in-house as well. We have global manufacturing facilities today that are allowing us to reproduce the turnaround time similar to what we're seeing with our existing commercial products. We think that's going to be really helpful. We know that with multiple myeloma today, at least in our discussions informally with centers, they want that rapid turnaround time that we're going to be able to bring. We also have a strong global footprint. We're in a number of countries today, 28 countries and growing.
We have 530 authorized treatment centers around the globe and we'll continue to grow that between now and 2026 when we launch. We would expect to have an even broader footprint at the time of launch. I think if you couple each one of those things, the relationship with Arcellx and Kite is a really good one in bringing forward what we think is a truly innovative product into the market most effectively.
Not that this is going to happen, but maybe we'll just do a theoretical. Let's say as you get more patients and more follow-up, you do start to see some neurotox events. Do you still think, how do you think you would compete on more of the Kite turnaround time and global footprint if the products ended up being more similar than different on efficacy and safety?
Maybe I'll answer it that we have today dosed 150 patients. We know that those long-term neurotoxicity events usually occur in the first 30. Frankly, by 90 days you're seeing those. We have 150 patients, a majority of them beyond that time frame that we haven't observed neurotoxicity. Of course, we're going to continue to watch. Patient safety is most important to us. We do think that there is a difference. Not all CARs are created equal. There is a difference between the constructs. We'll continue to look for that. We feel the hypothesis that we're exploring today is that we have a unique D-domain binder. What we've observed, we've had a chance to look at our anito-cel construct. We've made the other two constructs. What we see is a much faster off-rate.
As the D-domain binder binds, it has effective killing of the myeloma cells, but you do not see the immunotoxicity that we are observing with the other two. Our hypothesis is that fast off-rate matters. It mimics more physiological conditions. It also allows us not to see the inflammation, not to see the severe immunotoxicity. We feel pretty confident in this. Can we, could we observe delayed neurotoxicity? We are certainly looking for that. I do not want to pretend that we absolutely can say today we will not. We do think we have a differentiated binder that will make a difference as we come to market.
You're not even going to let me have the hypothetical and say I trying to isolate the strength of your commercial infrastructure.
I think.
I'm just asking there like how much upside you get if any product in your infrastructure.
Yeah. If you look at today in myeloma, we know about one out of 10 patients in that group are being treated. The class share is at 10%. We know that there's a big opportunity to be able to treat more patients. We know the data is profound and that physicians want to treat their patients. Patients want to receive the therapy. Having the largest commercial footprint, having turnaround times that are the best in the industry, we think is going to really make a difference as we come to launch. What we're hearing anecdotally, many of you probably speak to KOLs, is that they are looking for those tighter turnaround times. They're not getting exactly that out of the existing products today. It often means they have to bridge their patients or do a number of other things.
I know there's excitement about it coming. I can tell there's excitement just from the conversations we have, but also as we think about the iMMagine- 3 study and what we're seeing for interest and enrollment in that.
Can you help us understand? You talked about the global footprint. In terms of approval, how soon could you have global approval follow the U.S. approval?
Today we're talking about launching in 2026 in the U.S. Obviously every country is different. We would seek EMA approval. Following that, you also have to have HTA conversations. We're not necessarily committing to what the time frame would be around the globe. Suffice it to say we will be filing in all of the countries that we operate in today in Europe as well as in Asia, Latin America, and in the Middle East.
Got it. Maybe let's talk about your current business, Yescarta and Tecartus. I think I wonder if you could contextualize the in-class competition. We know that you faced some headwinds from that last year. Do you expect to continue to face those headwinds into this year and in future years?
Yeah. What we're observing with in-class competition over the course of 2024, we saw one of the in-class competitors get three new indications: follicular lymphoma, mantle cell. We also see a new ALL indication. When there's new indications in oncology, physicians are always excited to try those therapies. We are seeing physicians interested in giving a try to the new products we have. We have a combination of the new indications. We've also seen with one of the in-class competitors improvements in turnaround times and manufacturing reliability. Today our reliability is at 96%. In the U.S., our turnaround time is 14 days. Outside of the U.S., it's 17 days. We are continuing to make those improvements. We are also seeing some of the in-class competition getting better with their manufacturing. Not quite to the level we're at, but improving.
I think it's a combination of both the new indications coupled with that and physician interest in trying these therapies.
Have you seen like an arc of like were there physicians that tried it out earlier? Are they coming back to Yescarta? I think the worry is they really like the new products and the services around that. And then we have that.
We have seen that. We have observed it globally. I just returned from Europe where we saw, without going into detail, a couple of the countries actually go from trying the new product to coming back. I think when we talk to them about what is it that brought you back, I think components are the reliability of the product. There is also a belief that the efficacy with Yescarta is strong. We are the only company today that has statistically significant overall survival. That is something that resonates. In the U.S., we are observing the same. It is early days right now. Many of these constructs are being tried today. We are seeing, I think the word would be loyalist, that come back.
Right. Let's come back to the U.S. on the core business. That is the Authorized Treatment Center capacity, which I know that you're diligently working alone, but also industry-wide to help expand. Is the capacity we have today in the system, is that sort of a zero-sum game? Do you, is there a negative impact, let's say, on Yescarta from people wanting to use an Anito-cel, for instance? Or how should we think about it?
We don't necessarily see it that way. I'm going to break it down into a couple of things. We have the authorized treatment center footprint that we have today that we continue to grow. We also are looking at, we've shared, bringing community practices up and being able to either, if you're in a smaller community practice, that you would be encouraged to do referrals. We have a whole education component around that. There's a lot happening at an industry level around that education as well. We also have, for the large integrated community practices, a chance for those practices to actually deliver CAR-T. I think a year ago I was hopeful that this would happen quite quickly.
What we found out, maybe I can break down the dynamics there, is many of these large integrated practices are located within a hospital, next to a hospital. They already have a hospital relationship. What it requires to deliver CAR is that they formalize that relationship. Part of that is sharing the economics. The conversation between the community practice and the hospital working through that sharing of economics did not go as quickly as I had hoped. It takes a little bit of time for them to establish that relationship. I think the second component that goes along with that is FACT accreditation. Today some of our national payers tie reimbursement to FACT accreditation. FACT was started as a very important accreditation that is linked to transplant. As we know, CAR-T is not transplant necessarily.
If you're sitting in a community practice, we had one of the large practices say to us, we want to leapfrog transplant. We think transplant isn't going to be here 10 years from now and that CAR could replace it. We want to become a CAR-T center, not a transplant center. Today the way FACT is set up, you're both the way in which the accreditation runs. We have a great relationship with FACT. We're working at an industry level between the Community Oncology Alliance and FACT to really create a modular accreditation for CAR-T. That's something that will be piloted hopefully the second half of this year across three large practices. Once that's piloted, it can be refined and then rolled out more broadly. That FACT accreditation becomes really important. In parallel, we're not waiting for that.
We're having conversations with national payers to really educate them on the difference between CAR-T and transplant and why FACT accreditation shouldn't necessarily be the only link that they're drawing as to why they would reimburse. Those are the components that we're working on. There's a number of other things with making community practices successful that we are working at either as Kite or at an industry level to make that happen. I'm highlighting kind of the big three things that we're looking at. Now let's talk about what we can do. Part of the pieces that we're thinking about at Kite is how do we create constructs that enable outpatient delivery? That goes to the bed question or are we at capacity? Whether you're in a community center or an academic center, how do we make these therapies outpatient?
What does outpatient mean in CAR? It's very different than kind of how I would have defined it prior to working in CAR-T. Outpatient means that the therapy can be delivered and then the patient can go home. If the patient has a CRS event or an ICANS event, they can come back into the center for a couple of days while that resolves or just to be observed. If it's fever, they may be observed for eight or 10 hours and then sent back home. It's getting the patient closer to home, right? No patient wants to travel three hours for delivery. We're working at each level to say how do we create constructs that have that safety profile. If I give you examples today with Yescarta and Tecartus, we're seeing about 35% of centers being using it in the outpatient setting.
We know with an anito-cel, because of the onset being at four days, it's ideally situated to be an outpatient therapy. We studied that in iMMagine-1 in about 10% of the population. We are studying that in an even broader population, including community practices in iMMagine-3. Really looking at how could an anito-cel be delivered in the outpatient. All of the constructs that we're coming forward with as next generation constructs or new approaches, let's say in autoimmune or solid tumors, we're thinking about that outpatient mindset. How do we create the level of efficacy we want to see with autologous better than the products we have today, but also have that safety profile that it can be delivered in the outpatient?
It is each one of those pieces that are going to help us unlock the community and unlock these therapies being delivered closer to home. The last piece is the regulatory components of it. As you know, some of these products have REMS. Others are now being approved without REMS. How do we approach the REMS piece and how do we approach the 30-day follow-up of those patients? What you have seen is changing care, at least in the last six months, is now patients who are treated can actually move not 30 minutes or an hour from the center, but they can be further away from the center and actually receive care at their home practice. We are working through some of the logistics on that from a care model.
Wait, so that actually changed regulatory-wise?
Regulatory-wise, you can now be a little bit further away. They still believe you can make it back to the centers in time. Or you can be at an approved authorized treatment center closer to your home.
Are those the same ATCs like FACT accredited? Or is that a different type of approved center?
They could be. Let's say you end up receiving your care in New York City, but there's a FACT accredited center in Central New Jersey. You could actually get a portion of your care at the FACT accredited center. We want to get to a place where we have more centers that have this modular FACT accreditation. It's not just transplant units.
Got it. People can go back and sort of.
Correct. They can receive their therapy. They can receive their therapy close to home.
Close to home.
Yeah.
You said it really quickly. You said Anito-cel has the ideal outpatient with the first onset.
It really does.
I wonder both from the anito-cel perspective and as you're designing new constructs, what is the sort of target threshold on safety to really enable outpatient? What are the elements?
The elements are you want patients to be able to receive the therapy and have a little bit slower onset. As you think about the rapid expansion of the cells, how do you have the expansion, but not so rapid that it has a punch right up front, but that you still get to those peak levels you're looking for? That is what we see with anito-cel. By day four, that is when you start to observe CRS events or ICANS events. If you think about the 86% of the patients that have grade 1 CRS or no CRS at all, they would go in and be monitored for their fever and probably sent home, never admitted to the hospital, but rather sent home after the fever subsides. We have some hospital systems that are using watches that essentially monitor your fever.
They can tell you when to come in or not. You have triage units. That is a component of the care. You have four days where the patient can go home, return to regular life, and then come back in. Part of that is getting a second DRG code if you think about the U.S., what they are looking for. That is how they are defining kind of that outpatient setting. Ideally, the patient would be able to go home for some period of time. They would have low grade 1, let's say, CRS events as a majority of what their challenges are when you are saying what is the ideal profile. Obviously low ICANS.
When you design new constructs, how do you design for that kind of profile?
Yeah. I’d love to talk about our bispecifics because we thought a lot about that in the bispecific design. We have essentially one arm of it is a CD19 with CD28, so Yescarta, essentially. The second is a CD20 with 4-1BB. What it allows you to do is have fairly rapid expansion, so you get that what I call a punch, if that makes sense, to your tumor. Then you have the persistence from the 4-1BB. What we’re seeing in the phase one studies, and we’ll share that data later this year on those bispecific constructs, is exactly that. We have two. We have one that has a traditional manufacturing of six days. Then we have a second one that has three-day manufacturing, so we have more juvenile cells.
We can dose at one-tenth or one-twentieth the dose of Yescarta today, but still see the levels of efficacy we want to see with a much improved safety profile. Those are the types of things we're looking at.
Is the more juvenile cell, do you also get that slower expansion up? You get their juvenile on lower dose?
You do get a slower expansion, but you also have a much lower dose. I won't say slower expansion. You get a little bit slower expansion, not a lot slower. You also are dosing at such a 1/10 or 1/20 of the dose. That is helpful too, still seeing the same level of efficacy. Cells are very active.
I'm going to come back to the bispecific next question. I'm going to go back one more thing on the FACT accreditation. What are they looking for in these pilots that would validate that this is a process?
Yeah. I think part of it is they're designing it in a modular fashion that really goes to the institution and what they want to deliver. If I'm an academic institution, I can take the whole thing. Does that make sense? I want to do stem cell transplant. I want to do allo. I want to do CAR-T. Can I do the whole bucket? If you look at a center that's a community practice, they may only want to deliver CAR-T. They may not need the same level of infrastructure. Does that make sense? Even down to freezers that you would need on those various delivery models. It really is taking into account your infrastructure and your care model.
The pilot is to say, OK, this site has less infrastructure. And then making sure that.
They can successfully deliver it to patients.
Got it. OK, let's go back to the bicistronic and the CD19, CD20. A couple of questions. Just one, when will we see the data? And what kind of outcomes are you looking for to make the decision between the constructs?
Yeah. We have called it, I think, a bake-off, a horse race. We have three constructs. We have the two bispecifics I described. We also have Yescarta in a three-day manufacturing, which again, one-tenth or one-twentieth of the dose. What we are looking for is obviously improvements in efficacy as well as improvements in safety so that we can enable that outpatient profile. If you can imagine, we kind of have an idea now of what the other CAR-Ts in this space look like. We want to be better in both aspects.
How do your constructs compare to the other sort of leading bispecific? I think J&J has one that's had a lot of data. They licensed from Legend Biotech, for instance.
You're talking about the bispecifics?
The bispecifics. That's not necessarily bicistronic.
The difference is, and I probably should have started with this, the piece about CAR-T and the reason I joined Kite is the curative potential. Look, we have not seen in lymphoma since R-CHOP cures at this level. Although 60% of patients with lymphoma will get R-CHOP in the front line and have a great response and potentially be cured, another 40% are not. We know with Yescarta today that we can cure over half of those patients. With the bispecifics, we are not seeing that same curative potential today. To me, that is why I separate why I think autologous is a much better approach.
Actually, I didn't ask that. I meant the bispecific CARs.
The bispecific CAR-Ts.
Like how your bispecific is differentiated from the competing bispecific CARs.
I think the differentiation is really we spent a lot of time on the design looking at not just having dual targeting, but also having dual co-stimulatory domains and how we design it. What we've noticed is the dual co-stimulatory domains really play an important role as you think about safety and efficacy. We believe that you need the CD28 to have that impact on efficacy rapidly. We also recognize the 4-1BB is something that's super important to persistence. You'll see the data. You had asked when we'll share the data. We'll be sharing the data at Congresses this year. Our 363 construct study is fully enrolled in 753 and 197. We're continuing to enroll. You'll see data throughout the year. We're excited to share it. Please make time to see it. I'm super excited.
You've also announced, I think it's KITE-363 is a product you're going to take forward in autoimmune.
Yep.
I think until you announced that, it was still ambiguous whether you would bring an internal product or you'd license something. Why did you decide to do this internally and why that construct in autoimmune?
You know, we took our time in autoimmune because we wanted to make sure we understood the space and what would be the appropriate approach. Obviously, the Schett data is super compelling. Anybody who saw that and saw what they could do for lupus and lupus nephritis patients, it's a game changer. Many of these patients were hospitalized, bedridden. They have gotten their life back. Many of them in their 20s, right? That is really hard to see patients. If you think about autoimmune disease, this is a chronic disease. These patients are going to live with their disease for 30, 40, 50 years. The piece that autologous approaches give you is these patients are on therapy for 50 years of their life, 50 years of your life.
Can you imagine every day from when you're 25 until you pass away, you're on therapy for your chronic disease? The piece that the autologous constructs offer is a disease-free, treatment-free period. I won't say disease-free. I'll say treatment-free period. My hope is that we get to a point where we see these as actually something that can offer potentially cure and shift your immune system so that that can be the case. That isn't the data we have today. We'll keep studying it. You could imagine even two years, five years with no treatment is a game changer for these patients. CD19 data looks great, right? We've all seen the data. We were super excited about it as well. We also know in some of these diseases, CD20 plays a role in B-cell inhibition.
We know that because there's antibodies that are approved in that space. Ocrevus in multiple sclerosis, as an example, can be very effective therapy. Being able to hit CD19 and CD20 in some of these diseases we think is going to be really important. We also need to think about safety because in the autoimmune space, these patients, because they have chronic disease, are 90% of the time seen in a community setting, right? They're going to their local physician. They're not going to academic centers until they get absolutely refractory from the therapies that are available. How we create something that can be delivered in the community is the other piece that we have been paying a lot of attention to. We're excited to advance 363. We're really looking forward to what we saw in our phase one studies.
The data we'll share later this year in oncology looks like this is a great profile for an autoimmune therapy, particularly because we don't know how deep a response you need. We know in oncology you need a really deep response to be able to see curative potential. We think in autoimmune that as long as it's getting into the tissue, it may not need to be as deep a response. That is why the 363, the traditional manufacturing, made a lot of sense for us to move there. We will continue to keep looking at the external space. We're not going to lose sight of that.
We have five minutes. I'm going to put it out to the audience if anybody has a question. I'll move on. For the audience, as you think about autoimmune, is there particular indications that you're most excited about for your internal?
There are. We're studying. We just filed an IND for a basket study where we're going to be looking at lupus and lupus nephritis, myositis, and scleroderma. We'll be coming forward later this year with a basket study in neurology where we'll also be looking at MS and myasthenia gravis. We're excited about the possibility. Again, I feel like for some of those indications, having that CD19 and CD20 will be really impactful.
Got it. Maybe one more business question. We had dinner last night. I thought some of the most interesting comments, discussion we had were about the long-term business of CAR-T and sort of the barriers to entry. I wonder if you could talk about how you're currently thinking about the durability of this business for Gilead and what the barriers are that might keep this a pretty small focus that accompanies in the future.
We really see the cell therapy business as a long-term growth driver for Gilead. You've probably heard that from Andy and others. If I think about the business today with Yescarta and Tecartus in lymphoma, this is a really important business for us. We believe in 2034, we think that lymphoma market will be somewhere between $10 billion and $12 billion. We know that there will be growth there. Part of that is the pieces I talked about earlier on how do we unlock the use of autologous CAR-T more into community and getting patients closer to home. The work that we're going to do there, super important. If you think about multiple myeloma, we see that in 2034 as a $15 billion-$20 billion business. Why the difference? In lymphoma, patients are cured, as I said, 60% are cured with R-CHOP.
You really only have 40% of those patients progressing into second line and fewer into third line. In multiple myeloma, there are not necessarily curative options upfront or very few options. Some patients on transplant will have a really good response. You have a majority of those patients advancing to second line, third line, fourth line. For myeloma, we know those patients can go through nine or 10 lines of therapy and live for many years, over a decade, with their disease. Even entering with Anito-cel in the fourth line, we still see that as a really great opportunity for the company and a chance to start off with Anito-cel with our global footprint and our manufacturing and the great construct that it is to really grow that. We will come behind it really quickly with our second line study, iMMagine- 3.
We're also designing a study to go into the front line. We see, again, Anito-cel is another opportunity for growth. We see that market being $15 billion-$20 billion. All the work we're going to do in lymphoma today matters because we won't see the success in myeloma or in autoimmune unless we're able to unlock some of the things we talked about. Autoimmune, as you think about expanding, starting similar to how you approach it in oncology in that refractory setting. How do we continue to expand into earlier lines is something that market shaping is going to matter, what we do in oncology and will be directly applicable to what we see there. We have a number of—we did an acquisition of a company called Tmunity Therapeutics, which was looking in the solid tumor space.
We have studies ongoing there in GBM and neuroblastoma. We're also looking at other solid tumors. We think that solid tumors are tricky. This takes a lot of work. It's going to require two or three targets. We're looking at armoring and decoys. We have an opportunity to advance some solid tumor programs too in the clinic today, as I noted from Tmunity, but more coming in the future. That's autologous. We also know that there's other approaches in this space, whether it is allo in vivo. There's a lot of exciting things heating up right now. We continue to keep our eye on that as well. We either have some that we're doing through collaboration, some we're doing in our own internal research, as well as just keeping an eye on the external landscape.
We see this again as a long-term growth driver for Gilead and see the ability to move beyond just blood cancers, which is, you know, if you I will say that I was a skeptic five or six years ago. It's super great to be at Kite. I was wondering myself, was it going to have the curative potential? Were you going to be able to do this beyond blood cancers? It's great to see the data we see today in autoimmune and solid tumors.
The infrastructure you build in the community, those are in oncology. Those are oncology practices. Would that apply to Rheum? Or it's more about that model replicating it for Rheum or neurology?
It's about in the long term replicating the model. In the near term, what we found is that entertaining centers that have strong relationships between oncologist and their rheumatologist or their neurologist or those CAR-T treaters who have enough foresight to say, this looks really great in lupus, and I'm going to go down the hall and introduce myself to the rheumatology practice is really important. As we get our clinical trials up in the existing authorized treatment centers, what we're finding is we want the centers that have that rapport, that are willing to just say, I'm not an oncology treater only. I'm going to establish a relationship with the neurology unit, with the rheumatology unit. Long term, these patients are seen in the community. Being able to replicate what we learn in oncology to those practices will be important.
The therapies have to get safer, right? Safer and safer so you do not have lymphodepletion down the road and that you have an opportunity to truly deliver these in a community setting.
Do you have anything on the horizon on not using lymphodepletion or using reduced lymphodepletion?
We have ongoing efforts from a research perspective in that space.
Awesome. We went a minute over time. Thank you so much.
Thank you.
It's always a great conversation. Thank you for everybody's attention.
Thank you.