Commercializing CAR T Cell Therapy With Legend Biotech's Alan Bash

On this week's episode of the Business of Biotech we're speaking with Alan Bash, President, Carvykti, at Legend Biotech, about how Carvykti became a blockbuster, category-leading CAR T therapy for multiple myeloma. Alan talks about manufacturing and delivering an autologous cell therapy at commercial scale, Legend Biotech's partnership with Johnson & Johnson, lessons he learned at Bristol Myers Squibb, Checkmate Pharmaceuticals, and ZielBio, and his strategy for growing Carvykti's patient footprint and facing new competitors in the market.  

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Transcript

Meet Alan Bash And Carvykti

Ben Comer 0:04

Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm speaking with Alan Bash, President of Carvykti at Legend Biotech. Alan is an experienced executive and company leader. He began his career with a 22-year stint at Bristol Meyers Squibb, working in various product and commercial functions, and then served as CEO at both Checkmate Pharmaceuticals and Ziel Bio. He joined Legend Biotech in 2024 to oversee Carvykti, a J&J partnered CAR T therapy for multiple myeloma, first approved by FDA in 2022. Carvykti is a blockbuster product, meaning that it's a product with annual sales revenues exceeding $1 billion, but new competition from other products may be just around the corner. We'll discuss Legends partnership with J&J, how to grow an autologous cell therapies footprint and increase patient access, and how the company thinks about late stage competitors potentially entering the market. Thank you so much for being here, Alan. Great to be here, Ben. Uh before we uh get really started in earnest, Alan, I noticed uh at the bottom of your LinkedIn page uh that you were uh once upon a time a USA Today reporter. I believe that was in the 90s.

Alan Bash 1:23

Uh can you tell me a little bit about that experience? That's right. That was my first job out of college. I was a newspaper reporter. Uh I like uh I like to say that I had the best beat in the in the industry because I covered the television industry. So I got to meet celebrities from from TV and and and film. And that was I wrote about it for the for USA Today, which is everybody's favorite paper when they're traveling in a hotel. What a great gig. Yeah, it was it was it was it was a lot of fun. Um, you know, some of the you know, some of the late night hosts, David Letterman and Jay Leno, or folks I got to meet, and you know, some of the some of the TV shows that were filmed on the New York lots. So um it was it was a great gig for a young person.

Ben Comer 2:04

All right. Well, um you didn't stick with it though. You uh entertainment was not the beat you wanted to to pursue forever, I suppose. You went to Columbia Business School uh and then into the life sciences sector uh with BMS. Why uh why the drug industry? Um what interested you about the sector initially?

BMS Rotations And Checkpoint Inhibitors

Alan Bash 2:24

When I went to business school, I really got enamored with this concept of a mission-driven industry. And I had a number of colleagues and professors who had been working on boards of various companies. And, you know, I just got very excited by the prospect of being able to work in an industry that was obviously profit-focused and business focused, but also at the same time had a very core mission in terms of helping patients and improving improving health. And so um BMS was a wonderful company to join. I was I went through a leadership development program there, uh, worked through various commercial roles, you know, throughout all the various areas where BMS had uh a commercial footprint or a therapeutic area of focus, I had a chance to spend time on. And it was just an excellent way for me to see the pharmaceutical industry kind of at its best, if you will. And then, and then and we can talk about it. I I ended up transitioning to smaller companies. But uh, you know, that's why I joined BMS and that's why I had such a uh you know a rewarding career there.

Ben Comer 3:25

On the leadership program at BMS, uh, was that something you know that that they identified you for and asked you if you wanted to be a part of? Was it something that you kind of applied for? I'm just curious, you know, how you got in. It sounds like a fantastic program. And I know other uh big pharma companies have have similar programs as well, but I'm just curious about how you got kind of hooked into that.

Alan Bash 3:48

Several companies have these types of programs. And yeah, I was fortunate enough to be selected for it. It was a class of of new new recruits, if you will. And each year, uh, you know, the company would recruit a new set of uh candidates from various business schools. And I think even till this day, um, BMS and other large pharma companies have this type of program. I think it's really great because when someone's starting out, you don't really know which part of the business you're interested in, whether it's marketing, sales, market access, market research, uh analytics. And I think for someone to get a flavor, and it was a rotational program where I had a chance to move through different roles over the course of three years, uh, it really gives you a broad view on the business.

Ben Comer 4:30

Yeah, that's uh that's really interesting. So you you got to kind of bounce around in commercial was it pri was it uh like commercial functions, mostly commercial functions, it sounds like, yeah. Okay, and so then you you I mentioned in the intro you were at BMS for for 22 years. Was there, did you through that program uh identify you know a specialty that you know was particularly compelling for you? Or or what else, I guess, would you say about um you know that that 22-year experience there?

Alan Bash 5:00

If I if I look back on that uh that part of my career, the the most important aspect for me and the biggest highlight, and frankly the most rewarding for me was working on the checkpoint inhibitors. So Bristol Myers Swibb had the CTLA for Uruvoi checkpoint inhibitor. That was the sort of the first one. And then came the PD1s, right? And obviously today, if you look at the marketplace, Keytruda is the top-selling drug. I think maybe now being eclipsed by some of the GLPs. But from an oncology standpoint, uh the PD1s really revolutionized the treatment of cancer using the body's own immune system in new ways and expanding it to so many different indications. And I was very fortunate to be part of that journey. We had Opdevo, which was the PD1 that that that was the main competitor to Keytruda. We also had Eurovoy. We worked on the combination of the two. We were expanding it into new uh new geographies, new indications, earlier lines. So it was in the adjuvant and periadjuven setting. So there that for me was the best part of, you know, uh, you know, when I think about my career there, that was my favorite set of roles, which is working on the immune checkpoint inhibitors.

Jumping To Biotech And Deal Reality

Ben Comer 6:14

Yeah, yeah, absolutely. And then um, at what point did you decide, you know, that you wanted to uh to to dip a toe in in biotech and and move into company leadership? How did that come about?

Alan Bash 6:26

Well, you know, I I I was thinking about it for quite some time, and the opportunity presented itself for me to, you know, at some point, you know, in any career you get a little bit too comfortable. And and you know, you're you're you're coming to work every day and you're saying, this is great. Um, but the other side of you is saying, you know, it's you're getting a little too comfortable, Alan. You know, there's no there's no growth in the comfort zone, and there's no uh comfort in the growth zone, as they say. Yeah, so you know, so so I really wanted to try something different, you know, and uh and so uh I was, you know, I was recruited to become the CEO of a small public biotech in Cambridge, Massachusetts, Checkmate Pharmaceuticals, that, you know, for in terms of the check-woon inhibitors and working on um the adaptive immunity side, this was working on the innate immunity side and complementary mechanisms to the PD1s. Uh and so check wound pharmaceuticals, uh, checkmate pharmaceuticals was a great place for me to explore the world of biotech and sort of the the ways that smaller companies collaborate with bigger companies. And in fact, Regeneron was one of the companies that had a clinical collaboration with Checkmate. Uh, and I was not there too long for a period of time, but Regeneron came along and saw our data and got very uh excited by it and ended up uh purchasing Checkmate. Um, and uh and so that was a good outcome for you know a small biotech that had been you know looking for its its next uh stage.

Ben Comer 7:54

Yeah, absolutely. What could you say, I guess, about your role in that sale? I mean, was it was it something that you were negotiating with Regeneron? Obviously, they were they were partners maybe uh before you uh started, you know, took the lead role at Checkmate. I'm not sure. But um well, let me ask this. You know, what was the what was kind of the most eye-opening thing about moving from from BMS in into biotech? And then what can you say about uh the experience of of that uh Regeneron acquisition?

Alan Bash 8:27

Yeah, I was gonna say a couple things. First of all, you're absolutely right. Regeneron had a clinical collaboration with Checkmates. So um this predated my joining the company. And in fact, uh while I was there and it was only a short period of time, uh, it really moved very, very quickly. They saw our data. Uh we were able to conclude a deal with them um fairly rapidly. A number of, you know, my team members were heavily involved in that, or head of BD, uh, they're head of B D. Uh and really it was, you know, and then to link it to your other question about the experience, you know, for a small company that had basically one program, you know, in the clinic, you know, you're really at a crossroads. Are you going to try to get more money and invest and go beyond sort of where you are today? Um, or are you going to try to do an acquisition or you're going to try to do some sort of partnership? If you partner your lead asset, you know, do you have enough value in the pipeline? So for small biotechs, it's all about cash runway. And so we were always thinking about how much cash runway we had, and that was forcing strategic choices. And that was part of the calculation to do a deal with Regeneron. And so I think that was the biggest learning for me. You know, in big pharma, you never have to worry about that. You have to deal with budgets and PL. But, you know, in small biotech, cash is oxygen. And if you don't have that runway, then it really forces your hand in different ways. So that was, you know, I think an obvious learning for those of you who are in this business a long time. But for me, coming from big pharma into small biotech, that was the biggest takeaway.

Ben Comer 10:03

So uh Regeneron took out checkmate. Uh, you then went over to Zeal Bio as a CEO, I believe, right? Um what can you tell me about that company?

Alan Bash 10:14

That was an interesting company because that was looking at novel targets for cancer on certain types of cancer, a protein that was expressed on the cell surface. But it was very early. We did have a clinical program, but the science really was still evolving. And to just kind of be brief on the story about zeal, at the end of the day, that was a situation where the science did not progress sufficiently enough for us to have conviction around the targets that we were pursuing. And frankly, our investors couldn't get conviction around it. So as we went out to try to raise more money or get more money from existing investors, you know, it always comes down to the science. And they looked very, you know, carefully at the science and they said, you know, we just don't have enough here to feel comfortable about moving the company forward. And so we made a difficult decision. I recommended it to the board. The board accepted it that we needed to, you know, wrap up operations and fold down the company. It's unfortunately a storyline that happens to many, many uh small biotechs. Absolutely, yeah. Limited cash, you know, limited shots on goal. You have to take some bets. Sometimes it works out. We always like to see the ones that kind of made it through the gauntlet and say why they were so smart. But um, you know, for unfortunately for small biotechs, again, it's it's the bet that doesn't win that is is more often happening. And and so, you know, we're we we are we are only as good as the science, you know, you know, can can deliver.

Ben Comer 11:40

Yeah, absolutely. And you know, making that choice, you know, you you submitted this proposal to wrap up operations, which couldn't have been an easy decision to make, but it you know how much worse would it have been to continue kind of treading water and and progress it, trying to get more money in when ultimately, you know, it it it became obvious, it sounds like that you weren't going to be able to progress it. So, yeah, I mean that's that's a tough but critical decision, I think.

Alan Bash 12:06

It's it's a tough call. And and I think the existing investors for sure appreciated that because you know they they need to move on at some point too. Uh, and so this was this is the the best possible outcome given the circumstances.

Ben Comer 12:18

Yeah, and getting to that decision, you know, sooner than later obviously is is the best way to go. So um uh that was zeal bio. What what circumstances brought you to to Legend?

When Science Fails At ZielBio

Alan Bash 12:29

Well, yeah. So if I connect, you know, I was I was in a large pharma company for many years. I did, you know, two very small biotechs, and I personally was looking for something, you know, in a happy medium. And actually, a Goldilocks company. The Goldilocks company, exactly. And if I think about Legend, you know, Legend is an extremely unique position. You know, it's a small to mid-sized pharma company, it's a public company. We have an approved therapy which is doing you know extremely well in the marketplace today, and I'm excited to tell you more about that uh in terms of Carvicty. But we also have you know $900 plus million dollars in the bank. We have a pipeline, we have a large workforce, we have an established set of capabilities. So this isn't a small company where one trial is going to mean that you know the the demise or the fate of a company, but rather it's a company that has not only an approved therapy, but a pipeline, it has resources, but it's small enough. You know, we we you know we we absolutely operate the way a biotech, you want a biotech to operate, which is small, very fast decision making, working quickly, focused on the science, delivering value to customers as as as quickly and as efficiently as possible. So it it does feel for me, and I think for a lot of employees, like that Goldilocks situation where you had the large pharma potential, but you had the small uh company mindset.

Ben Comer 13:50

Now, were you familiar with um key executives or board of directors at Legend, you know, before you came, or were you meet out meeting everyone kind of for the first time? Uh what was that like?

Alan Bash 14:02

Well, you know, we always crossed paths with different people in the industry. So we had a lot of people in common, but I had not worked with the team at Legend. But again, as as as the conversations went, I started to realize we we had more connections, you know, as as we went.

Ben Comer 14:15

Well, uh let's let's talk about Carvicti. Uh, I mentioned in the intro it's a CART cell therapy for multiple myeloma. It was the second Car T approved for multiple myeloma behind uh BMS's ABECMA in 2021. Um it's been called a functional cure, and it's the current leader, I think, in sales and market share for this modality uh Car T in this indication. Um drug launches, and this is a big windup, so bear with me, Alan. But you know, drug drug launches have gotten a lot harder in recent years. You know, what what do you think are are some of the contributing factors to to the commercial success of Carvicti so far?

Why Legend Is The Goldilocks

Carvykti Launch And Blockbuster Data

Alan Bash 15:00

Yeah, and so just to put some some facts around that commercial success. So we just had our quarterly earnings call for Q4, and Q4 of 2025, we had sales of $555 million. And if you compare that to any other CART on the market, that's by far and away the largest selling CAR T across all the CAR T spaces, you know, lymphoma, myeloma, and any anything else out there. Okay, across all indications. Across all indications, right, not just even in the myeloma space. Um, we're we're number one. And then you couple that with the fact that we have now treated 10,000 patients with carbicties. So since the initial clinical trials, and then through the original indication, which you mentioned was in 2022, through the commercial uh production and all the clinical programs, we have treated 10,000 patients. And that's just an incredible number. If you think about autologous CRT, we're taking patients' cells, we are bringing them to our manufacturing plant, we are re-engineering the T cells, and about a month later, we are re-infusing those same cells to the patient. All of that has to happen in exquisite choreography, and we've done it 10,000 times. So, you know, that that's a real high watermark for the industry, for the CAR T industry. And again, from here, we just continue to build and show that we can continue to scale even further. Now, now, just to answer your question about the launch, because I know that you're absolutely right, you know, launches are getting harder and harder. I think for Carvicti, when it was coming into the market as a late line treatment for relapsed refractory myelombs. Originally, uh the original studies were in fifth line or beyond. And that was the indication uh, you know, on upon which it was approved by the FDA and the MA in 2022. Uh this was it was primarily about the the data. I mean, the data was just a rock star. It it showed overall survival data, it showed long-term PFS data, um, and it showed it in a way that was with a manageable safety profile. And the efficacy, because at the end of the day, we're talking about patients with significant morbidity and mortality. They want to know if they have a treatment's gonna work, if it's gonna really prolong their life and get them off other treatments. The data, the PFS data and the OS data that was shown in that Cartoon 1 uh study was just by far and away better than what the original um therapy that you mentioned from BMS had in the market. And so that's really what made Carvictti take off. Um, and and and like other CAR T's, we actually couldn't keep up from a supply standpoint with the demand. There were waiting lists, you know, we had uh we had centers having to allocate what we called allocation of slots, and those were the early days of carvicting. Now now the story has completely changed. And I'm you know, I can we can talk more about that, but that was what the launch felt like. It was actually there was more demand in the market than we had supply.

Manufacturing Lessons From 10,000 Patients

Ben Comer 17:59

Yeah, and that's a difficult situation to be in. Patients waiting to get this, you know, therapy and and not being able to get it right away. I I did want to uh ask you to dig into this a little bit. You know, you've treated uh 10,000 patients now. Um, you you must have gotten, you know, and you mentioned you know exquisite choreography going into this autologous process for uh for administering the therapy to patients. Um what I guess could you say about learnings, you know, after thinking about you know, 10,000 patients done, now you've gotten into a uh a process that is you know successful and and works and is efficient, I assume. Um is there any, and I'm I guess I'm thinking about other leaders potentially, you know, out there listening and or developing autologous therapies. What uh what learnings would you say, Alan? You know, what tweaks did you have to make? What what fixes were needed to kind of get that process into shape where you could turn up the scale to that extent?

Alan Bash 19:01

Yeah, and so and and just to be clear, a lot of this great work created me joining the company. Um, but I think there are a couple of important takeaways that that you know Legend has been able to demonstrate through this. And first of all, what one is the partnership with JJ. And you know, partnerships come in all you know, flavors and shapes and sizes. But what the way this one came about was that Legend presented the original data sets back in 2017 at ASCO. And basically, you know, as as people tell the story, you know, like the jaws just dropped in terms of the efficacy. And and J and J, you know, team members and leaders were in the audience and they got very excited by looking at this data, and they said, there's probably something here. Now, to be honest, and and this has been in the public record, I'm not saying anything new. There was skepticism because it was the data was from original, you know, from trials in China. And so the question was, you know, will this translate to to uh to an FDA filing? Can we replicate this in a global study? Is the data real? You know, that was a question that was on the you know, on the minds of people in 2017. And J and J very proudly likes to tell people that, you know, they went to China, they did the diligence, they looked through all the patient records, they did all the documentation reviews, and they brought the J and J, you know, they they brought the J and J rigor and they said, does this hold up? And they they came back with an you know exclamation point. Yes, it does. And so that's why J and J was willing to do a collaboration with Legend. Um and so I think your first to your first you know part of it is, you know, these small biotechs, they want to do everything themselves, and you know, that's the dream, but to scale manufacturing for autologist cartee, to commercialize in a highly competitive marketplace like myeloma, you know, where better could you be than to partner with the myeloma leader, which is JJ. And so the partnership is is number one a key, a key to success. That's that's for sure number one. And then the second thing I would say is you know, um any any given day um at a company, whether you're a small company, large company, or you know, wherever you are in the company, there's there's the day-to-day fire drills and then there's the the long-term planning. And I think Legend did a really good job of trying to navigate both. You know, it worked really hard to navigate the day-to-day, you know, um, you know, how do we deliver this product and and being trying to be receptive to customer needs and trying to improve the process um while at the same time thinking long term. So thinking about things like how are we going to scale and manufacture this in Europe? And again, through the partnership with J and J, um, it was identified that we we would start manufacturing construction and plans in Belgium, uh in the city of Ghent. And so now today, only a few short years later, when you know the teams originally were looking at just a a a greenfield, what they call a greenfield in the manufacturing world, right? It was just it was just grass um at a tech park. Now we have two facilities that are approved for commercial production in Ghent, supporting the European markets. Um they're they're they're near each other. One is one is called Obelisk, and the other one is a larger facility that we just got commercial approval last year for, which is called Tech Lane. And this is now supporting significant demand coming from the European launches. So I use that as an example to say, you know, you got the fire drills today and putting out the fires today and the short-term deliverables, and then looking ahead where you need to go and building for the future as well.

Building Capacity With J&J

Ben Comer 22:32

Yeah, I think it would uh maybe it's fair to say, correct me if I'm wrong, that uh Legend would probably not be able to stand up a lot of new manufacturing facilities in Europe and continue to expand uh patient access all over the world by itself. Is that is that correct?

Alan Bash 22:50

We absolutely absolutely uh you know value and rely on the partnership we have with JJ. And I think they would say the same thing. Uh and it's really about both companies bringing something to the table. Um, you know, we we brought a lot of the you know, the knowledge about the construct and about you know the therapy and about the science behind Carvicti. And then what JJ brought was the scale, right? The commercial scale, um, the the opportunity to do clinical development together, and then the manufacturing piece. So it really is that is that magic combination between what biotech and big pharma can do together.

How To Make Partnerships Work

Ben Comer 23:26

Yeah, and you know, as you mentioned, to its credit, J and J saw the potential of this product, you know, early on, you know, when there was when there was skepticism, uh I think everyone has sort of come around on on you know Chinese biotech at this point. You know, uh, but at the time, you know, J and J was sort of taking a chance. I I think it's uh unquestionable that it was a transformative partnership uh uh for Legend. You've just been speaking about it. Um, but I I wonder if there are any negatives uh about a large, you know, big pharma partnership partnering with the biotech. Uh and and you know, maybe you don't have to speak specifically to you know gripes with uh with J and J, but what you know, what what would you say for company leaders at biotechs who you know caches oxygen, as you said, they're trying to progress assets, looking for funding where wherever it may reside. Uh what would you say uh to those uh leaders um as far as you know things to consider or maybe to watch out for uh in a partnership with a a much larger company, understanding that you know that they're being they're able to offer things that you know that you couldn't do alone?

The Patient Journey And Outpatient Care

Alan Bash 24:40

I've been in a lot of joint ventures. I mean, a number of the products that were at BMS were joint ventures as well. There was a very large um anti-platelet category, and Plavix was uh Clipittegro was was the market leader, and that was a partnership between BMS and Sinofeed, for example. Um, and so so in any partnership, uh you really have to make sure it's clear about what each party is bringing to the table and have open communication, good governance, um, building trust among the parties, and making sure that your values and your goals for the product are aligned. Another product that I worked very closely on throughout my years at BMS was an anti-platelet um uh Eloquist, excuse me, an anti-coagulant Eloquist, which is a partnership with Pfizer, which is one of the largest products in the marketplace today, um, helping millions and millions of patients. Um, and I remember the early days when BMS and Pfizer were getting together around just setting up the foundation of a good partnership. And we had similar goals for and our vision for the product. Same thing with a small biotech. You know, they sometimes have their baby, right, their molecule or their program, and they're worried about sort of what it's going to mean with a larger pharmaceutical partnership. But again, I think if you hold true to what you want the product to be in your vision and you find a partner that shares that vision, but then can bring the capabilities, the resources, the expertise in certain areas, I think that's where, you know, it's a starting point for success. Then, you know, you get into the partnership. And, you know, I would be lying to you if I said every day was roses and you know, flowers with the partnership. We always have debates, you know, and we have discussions. But at the end of the day, um, we have a very strong partnership with J and J that allows us to work hand in hand on looking at the long-term vision for carvicty. And the long-term vision is this is a one-time infusion that has the potential to bring cure to patients uh in multiple myeloma where the disease was never considered to be curable. Both companies are firmly committed to that vision that this can become a standard of care for patients in all lines of therapy in multiple myeloma. And together, we have the opportunity to fulfill that vision. I don't think either one can do that alone. And so, you know, we keep our eye on the prize, if you will, curing patients with myeloma. I mean, period, full stop. That's our goal. And so, you know, I think that's really a key part of the partnership with it, which is both companies. I can tell you very specifically, we were just in in discussions this week with with senior leaders at JJ. And again, we both reiterated our commitment that Carvicti is an extremely unique therapy that has curative intent, curative potential, and that we want to bring that one-time infusion to more patients.

Ben Comer 27:26

Yeah, I mean, it's uh it goes without saying that it's the significance of a one-time treatment. Um, I I was I am curious about how it's administered uh in terms of the setting and you know what the kind of patient experience looks like. Does a um does a patient have to be admitted to the hospital uh to receive carvicti?

Alan Bash 27:47

So carvicti has a really unique model. Um so what happens in the patient journey is as follows. Um at some point, the patient has been assessed to be relapsing on their prior treatments, and um the patient then um will basically be sort of a candidate for CART T. And right now, Carvicti can can can be um administered in certain authorized treatment centers. That's the model that Autologist CAR T uses if you look at other others in the industry as well. So we have 145 authorized treatment centers in the U.S. You know, they're they're scattered geographically, obviously, some concentrated in some large cities as well. Uh, and we have basically a footprint that enables us to say that 80% of the patients with multiple myeloma are within 50 miles of one of our treatment centers. Now, we think we can probably even expand that footprint, but that's where we are today. So a patient um is referred from their community physician where it's being treated at one of these authorized treatment centers. This includes sort of the large academic medical centers, like you would think about MD Anderson, Memorial Sloan Kettery, et cetera, as well as many, many community hospitals and regional hospitals as well throughout the country. They go for um an aphoresis, which means we extract from their, you know, from a vein in their arm the blood product that enables us to isolate the T cells. Uh, we take the T cells from from that bag of blood and we bring it to our manufacturing facility. Um we have the manufacturing facilities, as I mentioned, um in Europe, but for the US, for the U.S. patients, this manufacturing is done in New Jersey at our Rariton, New Jersey facility, um, as well as we have one other contract manufacturer in New Jersey. Um, but all those cells come to come to New Jersey manufacturing. Um through that process, we are then isolating the T cells, expanding the T cells, and then uh transducing these T cells to enable them to express on their surface what's called the CAR, the chimeric antigen receptor. That car is basically like a homing device that identifies the BCMA target on myeloma cells. And once those T cells are re-engineered, have the car expressed on their surface, they're now car T cells, they're considered manufacturing through a series of testing and release, and we make sure that the standards are and the specifications are met. We are then able to release that product back to the hospital. The hospital calls up the patient and says, Your cells are ready. The patient comes back in for their appointment, and it's a very short infusion time for them to get their cells back. Now, you asked about whether patients have to be admitted for to the hospital. Um there are um there's really an opportunity for to do this without inpatient admission. We look at across all of our um all of the claims data that comes in for carvicty, and we see that about half of the patients are having the infusion of carvicty done in the outpatient setting. Interesting. So you know it really depends on how the hospital wants to set it up. Um, you know, oftentimes the hospital, you know, for their own protocols, wants to have the patient stay overnight for the infusion. Um, but it's not required. And that's one of the big revolutions with carvicti, that you can do it in the outpatient setting, and that that enables more and more patients to have it done, you know, in in different types of settings.

Ben Comer 31:14

Um, carvicti is it considered a second line therapy at this point? You had you mentioned you have to refractory on on the initial treatment. So is it is it considered a second line therapy?

Alan Bash 31:25

Yes, yes, it is. So so it after after the initial trials were done in the later lines in the fifth line plus, one of the big you know, watermarks for for carvicty was the fact that we demonstrated overall survival data and then were approved in patients as early as second line. So anyone who has had a you know a um a progression off of their first line treatment are now eligible, those patients are now eligible for carvictis. So it's second line plus. And and one of the things that we're finding is that um we get better outcomes, whether it's efficacy, whether it's safety, and also in terms of the manufacturing of the cells, all those things are improved the earlier you get the treatment in your journey. So, you know, we we've demonstrated data and we had some data at the recent um American Society of Humatology meaning that it's pretty clear that earlier is better when it comes to treatment of CAR T.

Demand Growth Through Education And DTC

Ben Comer 32:19

Okay. And um, you know, your your job, your task is to expand the market uh for Carvicti. And uh I, you know, part of the reason I was asking about you know second line opportunity for for Carvicti is uh I'm wondering kind of just how you how you do that. You know, you're not out building new manufacturing sites, but there is opportunity to obviously expand the market for Carvicti. And so um I'm curious about uh Alan, what what you're focusing on, how you do that with an autologous car T therapy, you know, um what what your approach is to expanding this market? Are you doing things like DTC advertising, for example?

Alan Bash 33:01

Yeah, so so the way we think about it is expanding both the supply as well as the demand side, and and and as you said, um expanding the market in terms of educating patients and and capturing more patients who are eligible. So on the supply side, again, I I shared a little bit about this before, but uh we're very excited to say that we have the commercial production both in the US and Europe, and we're really supply unconstrained now. We have the facilities that will enable us to scale and grow the capacity as the demand grows. So we have now uh our turnaround time is down, our manufacturing success rate is up. It's about 97% of the time we're able to successfully manufacture the cells. So we really have a very reliable process now that's providing a good patient experience. And I would argue that we've got the best in class manufacturing. I know some of the competition out there likes to tap their manufacturing capabilities, but we've been doing this now for years and years with BCMA. We've treated 10,000 patients, and we have a manufacturing success rate that's 97% plus. So we're very confident in the ability to supply the market. Now let's pivot over to the other side, which you were asking about, which was the demand side. How do we continue to expand the market? This is all about education. This is all about awareness because you know, CAR T is sort of viewed, even if you've heard of it, and not many patients have heard of it, um, and even some of the community physicians are not quite familiar with it. Sure. If they've heard about it, they might think, well, this is sort of that very specialized treatment that only certain centers can do. That's the big gun. That's you know, where I go for as a last resort. I we're trying through a lot of education and working with our scientific partners to say we need to think about this this disease differently. We have a potential with a one-time effusion to give very long-term remissions, to get patients off of treatment, to give them the shot at a cure, why wouldn't we do this earlier? And in fact, the earlier we do it, the healthier the patients are, they get a better efficacy outcome, the safety issues are significantly mitigated, the manufacturing is improved, and you get patients who are, you know, as opposed to as one of the physicians said to me, you know, if I can give a patient years of being off treatment so they can travel and they can enjoy time, wouldn't I want to do that with a 50-year-old or a 60-year-old rather than with an 80-year-old? I mean, let's give the let's give you know life back to as many patients as we can. And so that's why um the earlier use is really something that is starting to take hold.

Ben Comer 35:46

So education and awareness, uh, what are what are the uh you know, what are the your tools? You know, the the arrows in your quiver for that. It's not, you know, as uh someone who's who's married to a high school science teacher, I I know that education can be a difficult process sometimes to to communicate. Um what you know what what what are you trying to what what tools are you using, I guess, Alan, to expand, you know, to generate awareness amongst you know physicians that that may not be aware of it or or aren't thinking of it as a you know a second line option, uh or for patients who may you know be uh you know don't really understand what a car T therapy is, if they even know what it is, and and and may have some reservations about you know such a a new new kind of process uh for for getting treatment.

Alan Bash 36:36

So, so to the to the uh provider community, and and that's specifically not only those who are in the you know authorized treatment centers that we that we that we stand up, but then also in the referring base, right? All the all those community physicians, there are about 3,000 HEMOG practices out there that are referring into um the major centers. Uh, we do some of the the traditional education and awareness. Ourselves and JJ have field teams that are dedicated to Carvicti, that are working on delivering the scientific information, that are doing the sales, that are doing the medical information. Um, we have nurse educators in the marketplace that are helping the nursing community understand how to navigate patients and how to how to manage patients. Um, we are also, and I know you asked this before, we are doing, and this is a first for CRART, we are doing direct consumer education and awareness. We're not doing it on the on the traditional TV programs you see a lot of commercials on TV. We're doing that through dedicated channels, we're doing it through streaming, we're doing it through a video on demand, we're using social media. These are all ways that um we are reaching patients. And and we're obviously doing it in a very compliant and thoughtful way. And the most important thing for us is less about carvicty, because again, we're uh we're already the leader. It's really about the fact that there is an option for patients who have relapsed on their exit, you know, on their current treatment to get a one-time infusion that enables them to have very good outcomes. And obviously, we communicate benefit risk, we do that in a very balanced way. Um, but the education is all about there's this option for you. In fact, we had we had a patient come talk to our teams recently, and it was really fascinating to hear her talk because her question to her physicians was um, not, you know, tell me, Doc, what's next, right? It was it was tell me what my options are. And if we could get more patients just to have that dialogue with our physicians, and then the physicians are prepared to present, well, you know, you could go on this type of therapy, you know, you could go on a PI, you could go on an IMID, we could recycle you through another anti-CD38, you know, there's this thing called biospecifics. But we you know, we also want to tell you about this thing called CAR T. Educate the patients about what it is, what you know, what their experience is going to be, what the advantage of having this treatment is in terms of it being a one and done, and then, you know, and then leaving it up to a shared decision making with the patient, their family, and and the physician, you know, that's a win. I mean, to me, that's a win, and and that's what we're shooting for.

Ben Comer 39:17

Well, there may be some additional options uh uh for patients in this category uh pretty soon of pipeline competitors. I had Cindy Paretti from from Kite on the show recently. Of course, the big news uh in late February is that Gilead is acquiring Arsellix for uh $7.8 billion, I believe. Arsellix and Kite are collaborating on a BCMA car T uh for multiple myeloma. It's in late clinical stages. As the category leader, Alan, how do you prepare for the pending approval uh of that product or other competing products?

Alan Bash 39:55

Well, we've been preparing for a long time for it. And whenever they do get approved, and if they get approved, we'll be ready. And in fact, you know, people have asked us about that acquisition. And I think you know, we we've shared that that really validates the value of this space, of the potential for the myeloma market to be transformed by Cartier. And for us, it's not a zero-sum game. There are about a hundred thousand patients across across the the US and developed markets around the world that are second-line plus. That's an enormous opportunity. You know, today we've only treated 10,000, so and that's longitudinally, right? So so we've only scratched the surface in terms of this market of 100,000 patients. And so um, you know, when we think about competition, we think about being ready versus competition, and I'll share a comment some of our thoughts about that. But we also think about growing the pie, right? Growing the opportunity for CAR T's to get to more patients through, again, um broader reach into the community, more awareness, um, driving the referrals, but then also bringing CAR T administration into the community setting, expanding it in more markets. Right now we're in the U.S. and 13 markets outside the US, some of the major markets in Europe, such as Germany, Spain, Belgium, Denmark, but we have plans to go even further beyond that. And so um expanding it geographically and bringing it, bringing access to CAR T to many more patients. Now, specifically as it relates to that competitor that you mentioned, um, and they just got a um a PADUFA data standard review, not a priority review, I should, I should mention, but a standard review um for um for the end of December, uh, we're very ready. And I think we're feeling really good about the fact that, you know, they're showing data in the maybe 100 to 150 patients in their clinical study. You know, it's intriguing, but we've treated 10,000 patients. So, and I think that the the you know, when we show sort of that, when we had that discussion to physicians, what we hear back is, you know, any new any new product is gonna get a lot of excitement. You know, that's that's the name of the game in oncology. People are always looking for what's next. But what they also want to know is, is this a tested treatment? What's gonna happen in the real world? We all know that in clinical studies things are very curated. There's there's a lot of um selection bias in the patients. Um, but but and especially in a space where we're where we're perturbing the immune system, we're revving up T cells, you know, we're we're re-engineering T cells. You really have to see what happens in the real world with real patients. And now, 10,000 patients later, we we I think we have a really good idea of what the AE profile looks like for a CAR T and the best practices on how to mitigate and manage that. And so it's the maturity of the day, the long-term follow-up, um, the efficacy that we've shown. I think these things are all going to really matter when we get a competitor.

Ben Comer 42:49

Great. Um, J and J has also has its own clinical candidates, which could uh, well, you tell me, potentially compete with Carvicti, I think. How how do you think about that possibility at Legend? And is it something that that you discuss with J?

Sequencing Versus Bispecific Competitors

Alan Bash 43:06

Well, you know, I I talked before about options, and more options for patients are always better. And there is a new option. Um, and J and J uh now has an approval for a combination of um Teclistomab, which is a B A CMA biospecific, as well as Dera Tumimab, which is their anti-CD38 MA. Um, the the Tech Dara combination, if you will. And okay, that's approved.

Ben Comer 43:30

Okay.

Alan Bash 43:31

Yeah, it just it just got approved actually very recently. Um great news for patients. Congratulations to my partners at JJ. And again, the way we think about this is options for patients. Now, the good news is um there's gonna be a place for both treatment modalities for patients in the second line plus, but um as it relates to carvicty, um, one of the things that's really important is the sequencing. And so the uh there's a there's a working group of Myeloma experts called the IMWG, the International Myeloma Working Group, you know, a set of thought leaders who get together and make recommendations for the treatment of the disease, like any other, you know, um, you know, disease category, we have these working groups. And the IMWG has recommended that when it comes to sequencing, that patients should be assessed, evaluated, and and if possible, get to CAR T first. BCMA CAR T first before a BCMA biospecific. And the reason is because the data shows that if you do BCMA biospecific first, you're potentially wearing out, if you will, and exhausting that T cell population, and you don't get as good of an effect with CAR T. In addition, that the INWG has commented that, you know, if you have the opportunity to give patients a one-time infusion, get them off treatment, as opposed to with the biospecifics, it's continuous treatment. You know, why wouldn't you offer that to patients and get more patients to that? So, you know, sequencing is really important here. I think, you know, Carvicti has a very strong position in the market in terms of its profile, in terms of this recommendation, in terms of the support we have and the data we have. And so, you know, welcome competitors, great news for patients to have options, but Carvicti is very well positioned here.

Ben Comer 45:21

Is there a possible world where Carvicti moves or another CAR T therapy moves into first line for BCMA uh uh multiple myeloma? And um, you know, I I think, and correct me on this if I'm wrong, I think the first line is what, chemo or or radiation? Uh or or what what's the first line? And it it would is that is that something that that you guys are are thinking about or even you know trialing?

Alan Bash 45:46

There are about 30,000 patients in the U.S. who are uh treated for newly diagnosed multiple myelum or first line. And we have two studies that are now uh fully enrolled, our CARTUTE 5 study and our cartitude 6 study looking at this um frontline population. It'll take a couple of years for the full data sets to read out, but the two the two trials are in two different categories, if you will. One is the patients who are getting transplant as their first line treatment, and so autologous stem cell transplant is uh the standard of care for patients in the front line. And so we're asking the question can CART replace stem cell transplant as a frontline treatment? So that's the CARTE 6 data set, but only about a quarter of the patients of the 30,000 patients get that. The three-quarters of the patients either are ineligible for translat because of their performance status or or are not planned for for transplant or or choose not to do it because transplant is a very difficult regimen. It's very difficult on the body. Um patients have to be hospitalized, um, they get high dose melphalan. Um it's a very, it's very toxic chemo to basically wipe out their stem cells so that you know the new stem cells can be reintroduced. And so um a lot of patients choose not to do it or are not clinical candidates. And so for that population, we have the Cartitude 5 study where we are looking at uh we are going against the standard of care, a triplet regimen for um with um uh with a data-based regimen as well as um Velcade and Dexmethasone. And so these are the these are the the uses in frontline that then we are seeing whether CART can improve upon in terms of outcomes.

Pipeline Bets On In Vivo CAR T

Ben Comer 47:33

Got it. All right. Um before I let you go, Alan, uh I I wanted to ask about Legends pipeline and and also your top priorities for 2026. Um so uh maybe first, what what are the pipeline highlights? You know, what are what are you excited about there?

Closing And Where To Subscribe

Alan Bash 47:50

Also, we we've been starting to talk more and more about our pipeline. In fact, on our recent earnings call, we shared our plans that this year in 2026, we will present for the first time clinical data for our In Vivo platform. And if you think about all the things we were talking about in terms of autologous CART, where we bring the cells to a manufacturing plant, uh, you know, make sure that the the cells are re-engineered and reinfuse them into the patient, in vivo changes the game. It's a complete disruption of that. It is actually using the body as the manufacturing plant. We do the in vivo injection of the lentivirus and and the and the and the ways to transduce the T cells in the body. We don't have to bring it outside, we don't have to have lymphodepletion, we don't have to wait a month. And then that potential treatment then is having the T cells express the right antigen on the surface, finding the cancer and killing it. Um we announced that we are going to present for the first time our clinical data in 2026 of our early in vivo programs. Um we're looking at it in non-Hodgkin's lymphoma as well as myeloma. And we are um starting those studies, and again, this is the great model that Legend has. We're starting those studies in China, and then um as we as we share that data, we will then bring those into um IND enabling studies in the US and then uh moving it into um global studies as well. So um that's that's a key highlight for our pipeline, which is our in vivo platform. Uh, we also have allergenic uh programs. So the allo part of CAR T, you know, it's other donors who are giving um their T cells or NK cells. Uh, and we have that as part of our program. We're also looking at solid tumors, not just you know, um blood cancers. Uh and also we are exploring autoimmune disease because there's been some really fascinating data that CAR T can actually do an immune reset for patients such as those who might have lupus or other serious autoimmune disorders. So the field for CAR T is really just exploding at this point. Um, we had the leader in autologist CAR T, but legend is not, you know, wanting to rest on its leadership position there. We're thinking about the future and and you know, whether it's aloe, whether it's other tumor types, whether it's other diseases, and very excitingly, whether it's in vivo, these are some of the things that we're exploring.

Ben Comer 50:10

Yeah. Well, um, that's excellent, Alan. Uh, it's uh it's a really interesting company, and um, I really appreciate you coming on the show today. Ben, thanks so much. This has been great. We've been speaking with Alan Bash, president of Carvicti at Legend Biotech. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and make sure to check out our new weekly video cast of these conversations every Monday under the Business of Biotech tab at life science leader.com. We'll see you next week, and thanks as always for listening.