Good morning, everybody. My name is Alex Hammond, and I am the biopharma analyst here at Wolfe, and today it is my pleasure to host Gilead Sciences. We have Cindy Perettie, who is EVP of Kite, a Gilead Company. With that, Cindy, thank you so much for joining us.
Very nice to be here.
Obviously, it is a really exciting time for Gilead on the cell therapy front. I think it would make sense to maybe kind of take a step back and think about what you have learned from YESCARTA and TECARTUS, and what you have been doing boots on the ground that is going to further kind of help the anito-cel launch.
Thanks for that, Alex. The piece that YESCARTA and TECARTUS have allowed us to do is set the foundation. Cell therapy is not a typical delivery model, so you need to build up a number of aspects. One is your authorized treatment center footprint. Today, at launch for anito-cel, we will have 200 authorized treatment centers in the U.S. If you think about launches that may have occurred prior to this, they would have had 30 or 40 authorized treatment centers, and that was similar to when we came with YESCARTA and TECARTUS. The second piece is our ability to manufacture the product, and that is no small feat as well. We have had the opportunity over the last decade to really build out our manufacturing capacity, as well as integrating vector capacity.
Anito-cel, we are now producing in-house, and we are looking forward to, as we come to launch, to be able to provide the same experience that lymphoma physicians receive from Kite on the myeloma space. What does that look like? We have today turnaround times between two and three weeks with our commercial products. We expect to have the same as we come to launch with anito-cel. We have 97% reliability on YESCARTA and TECARTUS. We published at ASCO this summer that we have 99% on anito-cel. That will change, obviously, as we continue to get more volume. But having the reliability, the rapid turnaround times, is something that is an opportunity for many of these centers who have not experienced it with the existing products, where turnaround times could be over a month, out-of-spec rates at 20%.
We are excited to build off of what we have done with YESCARTA and TECARTUS, the relationships we have built in these centers with the hematology divisions, and bring anito-cel.
I guess with that, I would love to hear your thoughts on moving from purely an academic center to a community center with some of the reduction of the REMS, and how important will that be to anito-cel?
It is really important. You can imagine the community is incredibly important to us. Today, 80% of cancer patients are diagnosed in the community. 80%. 80% of them are being seen in the community. Moving into the community is increasingly important. We will be launching anito-cel in the fourth line plus indication, and today, many of those patients are actually in academic centers. Our existing footprint we have today, the 200 centers, a majority of them are academic centers, but we have about 25 community practices, and we continue to build on that every year. But for the fourth line launch, we know that the authorized treatment centers that are academic are going to be where most of those patients are.
When we come out with our iMMagine-3 data in the second line plus, the community becomes incredibly important, and that's why you're seeing the efforts we're taking today to move into the community. The safety profile of anito-cel lends itself very nicely to be delivered in the outpatient setting and in the community, and so physicians are now going to get experience with that.
As you move into earlier lines, patients are also fitter, and therefore the safety profile is even
That's exactly right. You raised the point about the REMS. That can't be underestimated. When many of these products launched, including YESCARTA and TECARTUS, there was a REMS program, and that also can be difficult for patients to not be treated close to home. So the ability to reach patients in the community where they are is really important.
I guess as well, you mentioned the 200 active treatment sites as well. We have the lack of REMS. What do you kind of see as the hurdles or the barriers to the first year of launch? Because obviously more of a 2027 than a 2026 launch.
It is. Coming in as early Christmas gift. The things that were barriers in the past, you talked about the REMS program, that was definitely a barrier with the regulatory agencies in the past. The other piece, when CAR-Ts first came out, were that there weren't slots, right? So slot availability was an issue, so every patient maybe wasn't going to be able to get cell therapy, or physicians and patients had to wait for a slot to open. That's no longer the case. The capacity we have with our manufacturing today can serve YESCARTA, TECARTUS, and anito-cel well beyond the launch in fourth line, and certainly coming into earlier lines. So we feel very confident about some of those things that were hurdles in the past will not be hurdles in the future.
As we think about the label as well for anito-cel, I think PDUFA is what, December 23rd?
That's right.
Anything that we as investors and the sell side should be looking out for that will be particularly important to kind of help with the launch?
Yeah. I think there's a couple things as you think about launch of a new product. We have to turn on 200 authorized treatment centers. They are centers we work with today, but we are working with them now to contract to bring in anito-cel, and we can't complete those contracts per se until we have a labeled product to add to it. Once we've started to turn them on, in order for them to order, you have to have Kite Konnect is what we use in lymphoma. The same will be used in myeloma, but it has to be programmed into the EMR, so there's a period of time for getting that programmed on site. You have to go through formulary disposition as well, so getting on formulary. In some centers, that can be overnight.
In other centers, they only meet once a month or once every two months, and so getting on formulary will be important, and then getting that payer reimbursement. We expect, again, six month uptick of 80% of our authorized treatment centers coming on board. We also expect to have 90% of payers within the first year reimbursing, and those are the types of things we're looking at. Our goal is to achieve brand leadership within the first 18 months, and we're looking forward to doing that.
I guess another question with that as well is finding the patients, and these patients are obviously fourth line plus, they have a lot of tumor burden. How important is it to do debulking, and kind of how does that add complexity to the process?
It's important because many of these patients, as you said, are debulked, and we often see that cell therapy safety profile is indicative of how bulky the patient can be if they end up having CRS, as an example. In myeloma, particularly in the fourth line, you may find bulky patients. Patients may receive two cycles of essentially of bridging before they get their cell therapy. As I talked about that ramp-up and what it will take to get the authorized treatment centers up and going, patients identified. Once they're identified, they may choose to have to have bridging, which could be two months.
I know you're sharing additional data of iMMagine-1 at ASH in the coming weeks. Kind of set the stage of what we can expect to see there.
We're excited to share an 18 month, so 18 month minimum follow-up of our patients. If you think about the data we've shared in the past, we're continuing to get more confidence on durability. The efficacy and durability data will be shared at ASH this year. For those of you who saw the abstract, we're looking forward to sharing more about that data, but we continue to see those deep, durable responses. We're also going to share a safety update, and I get this question quite frequently from analysts, have we observed delayed neurotoxicities? To date, we fully enrolled our iMMagine-3 trial, so we've got between our phase I, iMMagine-1, and our iMMagine-3 trial, over 400 patients dosed with anito-cel, many of those with longer-term follow-up. We continue to feel very confident in the safety profile, and you'll have an opportunity to see that.
Our grade three CRS or ICANS rates continues to hold being less than 1%. There's a lot of opportunity to see that durability of safety and efficacy. We're also going to be sharing our PFS curves. We talk a lot about complete response. Complete response translates into your PFS curve, so having the ability to see the PFS curve, I think will instill more confidence. It's still immature, so what you'll see in the PFS curve is sort of a mature curve up to that 18 month mark, and then we'll have a lot of censoring for the patients beyond that. But we're looking forward to sharing the PFS curves.
You touched on a little bit on the safety, and obviously that's a huge point of differentiation, and I guess both in the fourth line plus, but how important is that in the second line plus?
Yeah, it is really important. If you talk to physicians and patients, right now what we are seeing for fourth line, to give you an idea with CARVYKTI, it is about 25% penetrated in fourth line for those patients that are eligible. In second line, that drops substantially to 4%. Why 4%? Why is not CAR-T penetrating in the second line? These patients can live for up to a decade.
In second line, if you have a patient and you are making a treatment choice, your choice could be that they get this amazing one-and-done therapy, but there is a 10% more or more chance of having a delayed neurotoxicity or enterocolitis. While you may have set the multiple myeloma at bay, those patients could get parkinsonism, they could get Guillain-Barré, they could get cranial nerve palsies. These are not resolving, and you cannot identify which patient is going to get that.
For a second-line patient, I think they are making that trade-off. We think anito-cel is going to be a great opportunity to have the potential to have these long-term durable responses without compromise, without the compromise of the delayed neurotox, without the compromise of enterocolitis, and finally, without the compromise of what they experience today on the manufacturing side. We think it is going to be a really important option, and we believe that we can grow that market. We believe having an option that has the appropriate risk-benefit profile for a second-line patient is really important, and that is what anito-cel is going to bring.
Wow, that is a perfect segue into how to think about iMMagine-3. That is fully enrolled now, and I think you guys have kind of made comments about a submission sometime in 2027?
Yeah, the earliest we could see the submission we have communicated is 2027. We are excited. We enrolled the iMMagine-3 study in June, so well ahead of schedule. Often you see with physicians, particularly in academic centers, they vote with their patients. If they like the therapy, your trial enrolls faster, so it was a good sign for us to see that enroll. We have dual co-primary endpoints, so the first endpoint that we could see is MRD in collaboration with complete response rates, and then we have progression-free survival. Progression-free survival is obviously event-driven, but we have an opportunity certainly to see the MRD and CR rates.
One of the questions we get all the time is the bispecifics have obviously kind of come out from an efficacy perspective better than expected. How do you kind of think about sequencing and the competition with these BCMAs?
Yeah, so I'm going to start by saying it's great for patients to have all these options. For those of you who have worked in multiple myeloma for a long time, there wasn't a lot of things to carry in the bag for the physician or tools to use with patients, so it's always good to have options. As you think about the market that we're entering into right now, in class, CARVYKTI is our main competition, and we've talked a little bit about the differentiation that we see there and our opportunity to grow. On the bispecifics, there's a couple things that I think to think about. One piece is that many of the community practices are starting to adopt bispecifics. They have to do step-up dosing. They're learning what it's like to deliver a complex modality. That's helpful.
Those community practices that have delivered bispecifics are now asking to bring CAR T on board. So the idea of having that complex delivery model has worked as we want to expand into the community. The piece that I would remind people of on bispecifics is that they can cause T-cell exhaustion. IMWG guidelines, which many of the global multiple myeloma physicians follow, suggest that CAR T is used in advance of bispecifics because of T-cell exhaustion. If you give a bispecific first, it's not as easy to do the CAR T, but you can do it the other way around. You can have CAR T followed by the bispecific and still get efficacy from both, and that's what IMWG criteria recommends. The other piece that I would bring up on the bispecifics is, it's early days.
I'm excited to continue to see the durability data, but the efficacy data that we're observing in bispecifics is anywhere from 30%, and I think there's one study that reported as high as 50% complete response rates. That is in comparison to 70%-80% on the CAR T side, so the efficacy difference is there. In addition, there's a different sort of profile for toxicities, and many of these patients, if you look at the trial, cannot receive these through progression. So there's pros and cons of both, but we think having a one-and-done option for patients with that level of efficacy, and the safety that we're observing is the right approach.
Yeah. So with new drugs kind of going into the market, there might be a differential kind of where CAR T shakeout
for the second line. Got it. Okay, that's helpful. I guess
CAR T first for the IMWG criteria.
Then I guess a natural follow-up question is on manufacturing.
This is something that you guys have talked about, this differentiating. Do you have the capacity to handle such strong potential uptake given physicians' clear interest in this drug?
Yeah. It's a conversation that we had quite a bit over the course of the last year as we looked at scaling up our manufacturing capacity, and we do. We feel very confident that we have enough to serve the market, irrespective of the type of bolus that we may see, and we're looking forward to launching.
How do you think about the U.S. opportunity versus ex-U.S., particularly as it relates to single-payer system versus the multi-pronged U.S. approach?
Yeah. What we've observed in lymphoma is very interesting. I've been in the pharma industry for about 25 years, and you generally launch in the U.S., have strong uptake, you move to Europe, and sometimes getting through payer reimbursement takes time, and you never quite see the same level of uptake, and you all know that because you're analyzing these. What we've seen in CAR T is exactly opposite of that. If you have a universal healthcare system with a single payer, once CAR T is adopted and distributed in academic centers of choice, it is used. Everybody refers their patients into those centers, and we see up to four times the volume outside of the U.S. that we do in the U.S., which is very different than other modalities.
Any thoughts too on the pricing as you think about anito-cel as it relates to, let's say, the competition, CARVYKTI?
Yeah. We don't comment on pricing, but we feel like we have a fantastic offering in anito-cel.
Maybe moving away from multiple myeloma, unless you have any other kind of closing remarks on how you think about the opportunity.
Yeah. No, looking forward to the launch, and again, just stressing, as you guys think about how you want to measure us, remember that uptake curve is going to take us six months to get all of those authorized treatment centers up and running, 90% of payer coverage in a year, and a brand leadership in 18 months.
Very excited for those 18 months. We've obviously kind of seen some new updates in the autoimmune space. How do you guys think about the risk-benefit of treatment in the autoimmune space, kind of given the recent patient deaths?
Yeah. The recent patient deaths are incredibly unfortunate, and nobody wants to see that happen, and I think the scientific community has taken a step back in making sure we understand why and that data. With that said, we have not observed that in the programs we have. Today, we have two programs in the autoimmune space, and we've been really thoughtful about our approach. When I say thoughtful, it's about doing dose definition and not assuming an oncology dose can work in autoimmune. It's also about looking at the lymphodepletion regimens, and that in the autoimmune space, we don't believe that the lymphodepletion has to be as strong as what you're using in oncology. We stepped back and took a very thoughtful approach before we started. We have two programs in autoimmune on the Kite side. One is a CD19/CD20.
We're excited about that because we know CD20 plays an important role as well in the autoimmune space. Then we have, after the acquisition of Arcellx, we also have anito-cel being studied in myasthenia gravis and myositis. The myasthenia gravis study is near fully enrolled, the phase I, so we're looking forward to seeing how that pans out. For CD19 and CD20, we have two basket trials, one in rheumatology where we're looking at four indications, and one in neurology where we're looking at four indications. So we'll have an opportunity to see this plethora of data. We know for CAR-T, this could be a real game-changer in autoimmune if you're thoughtful in your approach in moving forward. Why is that? These are patients who are on chronic therapy. My sister is a multiple sclerosis patient.
She's been on therapy for 32 years, and you don't get a treatment holiday. You are on chronic therapy, and many of these diseases looks like that. With CAR-T and having a one-and-done, you do have a chance to get a treatment holiday, and wouldn't it be great if at some point we can hit immune reset, and these are actually curative in the future? But providing that sort of optionality for a patient, even if it's four years, five years of treatment-free, is really important.
How do you think about the type of patient that would be best served here? Is it that the younger patient that is a little bit fitter, or is it kind of that later-stage patient where they have been on chronic therapy for quite some time?
Yeah. Similar to the approaches you have seen for CAR T in oncology, is similar to what we are seeing in autoimmune. You are entering in those patients who are maybe more refractory to existing therapies, have been on therapy for a long time, and then as we get confidence in the safety profile and the risk-benefit profile, you can move into younger, fitter patients.
I think in autoimmune, you have an autologous CAR T, an in vivo CAR T, and then a T-cell engager.
We do.
You have a lot going on. How do you kind of think about which therapy for which patients? How do we kind of think about the modalities fitting together, essentially?
Yeah. We see these modalities as complementary. Maybe I'll walk through each, and then I can talk about where you might even think about combining. In the autologous space, I just walked through the two therapies that we're studying right now. In the in vivo space, we're making similar therapies. For those who aren't as familiar with in vivo, this will be off the shelf, no lymphodepletion, so much easier for patients, particularly in the autoimmune setting. In both of those cases, the acquisition of Arcellx has helped us a great deal. Arcellx has these unique D-Domain binders, which is what's in anito-cel. These binders are quite small. They're about 100 base pairs, and we believe that what we've observed on the safety profile in Arcellx is indicative of this small, tightly wound binder.
In contrast, most of the binders, including YESCARTA and TECARTUS, are 500 base pairs in size. In order to make a vector, your rate-limiting fact in a vector is essentially real estate, and you can hold up to about 1,000 base pairs. If I use the CD19, CD20, they're 500 each, and there's your whole vector. You've taken the real estate up. With Arcellx, it gives us the opportunity with these small binders to actually put in additional targets. That becomes important as we start to unlock the autoimmune space and understand what's possible. Our in vivo approaches, we'll be looking at similar to ex vivo, but we also have the opportunity to look at more antigens in one.
With gamgertamig, which is an acquisition that Arcellx made of a BCMA TCE, we're really excited about that, and it gives us the opportunity to potentially combine with the therapies we have today. We're going to be sharing data at ASH as well on gamgertamig, so I hope you get to attend that presentation. When I was speaking earlier about the concept of immune reset, this could be an opportunity where you could do this in combination with a T-cell engager and a cell therapy and truly reset that patient's immune system so they don't remember they have a disease.
That's very helpful. Thank you. I guess as well, if we think about in vivo CAR-T, do you see this replacing autologous longer term, or what's the position there?
Yeah. We see this as complementary as well. To date, with lentiviral vectors, those who've been in the gene therapy space, you can't redose, your body creates an immune response to the lentiviral vector. We know that patients may have disease throughout their life. For in vivo today, based on the science we know today, and that could change over time, these can only be dosed a single time for the integrating in vivos. Non-integrating, you can do multi-dosing. We believe that what you may see is in vivo move into earlier lines because of the delivery is much more ease and to be able to go into the community. But you would have autologous as the next set of therapies that you could receive.
That's helpful. I guess as well, I think it's interesting. Clearly, you have a footprint from an academic center for multiple myeloma, but how do we kind of think about in autoimmune disease? Obviously, you're potentially hitting rheumatologists that have obviously neurologists, little experience in the cell therapy space. How long does it take?
Yeah. This is exactly why, in oncology, our ability to move into the community is incredibly important, because it will be the same concept that you're seeing in rheumatology and neurology. Most patients are seen in the community. What we're seeing today, so in the clinical trials realm, they're partnering. The major hospitals that have a rheumatology department are partnering with the oncology CAR-T delivery group and delivering it that way, and that's how they're getting the experience. That will happen over time, but we need to have a way in which we can open this up.
That makes sense. Beyond anito-cel, obviously quite excited for that launch, where do you expect Kite's next kind of leg of growth to come from? Do you kind of see lymphoma coming back to growth?
Yeah. Today, we have communicated for YESCARTA and TECARTUS, we continue to face in-class and out-of-class competition. The next real growth driver is going to be the anito-cel launch. We're looking forward to bringing it forward in fourth line, and in 2027, it would be the earliest filing of the second line. We've kicked off both of our newly diagnosed studies, and those would begin enrolling early next year. Anito-cel, and we're also doing some exploratory work in smoldering. We have a lot of work to do in anito-cel, and we continue to see that as a growth driver. Today, the fourth line setting is a $3.5 billion market. As we move into second, we see that as a $12 billion CAR-T market, and as we move into front line, a $20 billion CAR-T market.
We have a lot of opportunity with anito-cel. We also have a full pipeline. We have a next-generation lymphoma product that we're studying. We just talked about autoimmune, so we have a couple plays there. Our in vivo portfolio, we are currently building out and have started IITs in China and look forward to getting phase I's going. Finally, we have two programs in solid tumors, so hepatocellular cancer as well as glioblastoma. We have a full pipeline, but the near-term growth is really going to be driven by anito-cel.
In terms of anito-cel as well, in terms of the newly diagnosed, would that be, let's say, you're enrolling now more of like a 2030-type launch?
Yeah. We haven't communicated the launch, obviously, or the timelines, and much of this is event-driven. But as you've seen with recent approvals of the bispecifics with surrogate endpoints like MRD, I think you'll start to see that evolve over time in the newly diagnosed setting as to what are the most relevant endpoints.
In transplant-eligible patients, obviously that does not come without its own risks. Can you kind of walk us through what those patients might encounter and why you could actually see a CAR T be a better opportunity or treatment?
Yeah. So today, for transplant-eligible, they're eligible because they're getting a transplant. They're referred in frontline into the academic centers from the community to receive a transplant. That is changing now with CAR T and all of the additional therapies, including the quads coming into frontline. So there's a real opportunity in frontline, and the way we've designed our studies is for transplant-eligible is to replace transplant with cell therapy. Transplant is fairly cumbersome, and CAR T is an easier delivery for these patients. So far, the durability data we're seeing in later lines are indicative of what we hope to see even better in earlier lines. So for the transplant-eligible population, our clinical trial today is you do an induction with the quad, and after the induction, you give CAR T therapy.
Those patients then go on to get maintenance therapy, and many studies are now looking at fixed duration on maintenance. In the transplant-ineligible, we are looking at doing something somewhat similar with induction of the quad followed by CAR T, but we are looking at MRD-guided maintenance. This is an important question because we're talking about a one-and-done therapy, and if the patient has to remain on maintenance therapy for three years, it's truly not a treatment holiday. So the ability to leverage MRD to understand if that patient needs to have maintenance is going to be an important question that we're asking as part of that trial.
For sure. I guess, how beneficial is it to you guys that you have a competitor that's kind of launching first and that can kind of take learnings from there into these new patient populations?
Yeah. As we talked about, there's an established fourth-line market today with 25% penetration that we think is a great opening spot for us with our authorized treatment centers. What we haven't seen with some of the competitors is their ability to move into earlier lines, and we think our safety profile lends to that. We're certainly taking a lot of learnings from the folks who have been there before us, but we also have a lot of tricks in our bag as well.
Very excited to see those. I guess really the last question for me is, what do you think is most underappreciated about the entire Kite company as a whole?
Yeah. If I think about Kite, the piece that's underappreciated is that CAR T, we thought, was going to be strictly in hematology for a long time, right? We've seen fantastic responses in cell therapy in blood cancers, but we haven't seen that translate. What we're seeing now is that translate. The underappreciated piece that we have is a very strong R&D pipeline and a very strong R&D team, as well as leading industry manufacturing. If you combine that, we have the ability to bring products in a more reliable way to patients. The acquisition of Arcellx, I can't stress with the D-Domain binders what it's allowed us to do and open up going after three antigen targets and armoring in a way that we wouldn't have been able to without that. So, those are the things I think that might be underappreciated.
Do you have a favorite child?
Oh, that's a tough one. I love them all, but I'm excited to see what we can do in GBM.
Perfect. Well, with that, thank you so much for joining us, Cindy. We appreciate it.
Thank you very much, Alex.