September 9, 2025 • 55 mins
“Once a scientist, forever a scientist,” says Legend Biotech CEO Ying Huang as he joins Bloomberg Intelligence analyst Sam Fazeli to share his unconventional journey from the lab bench to Wall Street and back to biotech leadership. Dr. Huang explains how a dream led him from equity research to developing one of the most important CAR-T therapies for multiple myeloma. They explore the science behind BCMA targeting, lessons from the pivotal Johnson & Johnson partnership as well as the company’s ambitions in allogeneic and in-vivo therapies.
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Speaker 1 (00:17):
Welcome to another episode of Bloomberg Intelligence Vanguards of Healthcare podcast,
where we speak with the leaders at the forefront of
change in the healthcare industry. My name is Sam Fazelli
and I'm a healthcare analyst at Bloomberg Intelligence, the in
house research arm of Bloomberg. I'm thrilled today to welcome
Yeng Huang, who is going to be talking to us
(00:38):
about Legend, the company of which is CEO. It's one
of those great success stories in biotech where they've gone
through what a lot of biotech companies when they start,
it's just a hope in their eyes they have a
product on the market, and not just any product, it's
a product that really has changed the narrative in treatments
(01:01):
of multiple maloma. So I'm really pleased to have being
here with us. Thank you Ying for joining us. The
conversation is going to be divided into three parts. Obviously,
a lot of it's going to be about a legend
and the products and the pipeline. But I wanted to
start offering first to just get a little bit of
your history. You have an interesting history of having been
(01:23):
on the investor side, having been you know, this is
the andlyss side and now the CEO of a company.
Tell us how that transition happened. How did you end
up on Wall Street? Tell us about your story, go
as early as you like, yours, studies, university, what drove you?
This is all very interesting for us.
Speaker 2 (01:41):
Yeah, first of all, thank you Sam, and thank you
to Bloomberg for hosting me and Legend. It's somewhat unconventional
career path for me to go from a scientist to
equity research analyst on Wall Street and then back to
the industry and now being the CEO of Legend. So
I was trained as a scientist. I majored in chemistry
(02:05):
in college. Then I came to the States to pursue
a PhD degree at Columbia University in New York City.
So right after I graduated with a PhD, I joined
a major pharmaceutical company named Sharing Plot, which is now
part of a market company following the acquisition. So I
was there for nine plus years as a medicinal chemist,
(02:27):
working on the bench and leading a group of scientists
working on projects mostly in cardiovascular and CNS disease areas.
Decided to go to business close to the end of
my career at Sharing plot because I developed a pretty
intense interest in the business side. So my original intention
is to go into business development or licensing using my
(02:51):
science expertise and the skill set I acquired from both
Grasco and Work and Sharing. But I took a detour
because that would before financial crisis. It was two thousand
and six, the large majority of my business school classmates
were coming from the banks, and I stumbled into an
opportunity in equity research. So I became a junior analyst
(03:15):
back in two thousand and seven working for about Tech Analyst,
and then I stayed because I found it so intriguing
to be able to talk to so many different companies
with so many different molecues targeting different disease. It was
just eye opening because during my nine year career sharing,
I worked on only three projects, while you know, sitting
(03:37):
in the stead of equity research challengls. Like I said,
all of a sudden, I saw so much science, so
much excitement on developing a breakthrough therapy. So I stayed
and I worked for twelve years on the street. Last
job being at BFA Marriage, where I was a lead
analyst and also managining director, covering the US by tech
(03:58):
sector for the bank. And in twenty nineteen, we had
a common friend between me and the Dance, CEO of
Legend Biotech. We had a conversation about how to bring
a private clinical stage about the companies to the public market.
And then a couple of weeks later, I got a call,
(04:19):
you know, there's an opportunity, there's opening here at the
Legend because they were recruiting a CFO. So I took
the plunge and I joined the company in summer of
twenty nineteen, and then we brought a company in public
in twenty twenty, and then later that year I was
appointed the CEO by the board for Legend. So that's
(04:41):
kind of like how I end up here?
Speaker 1 (04:43):
Did you have to move?
Speaker 2 (04:44):
Not physically because I went to school in New York City.
I worked at a farmer company in New Jersey, so
I've always lived in the state of New Jersey after
graduation from school, so I did not have to move physically,
you know, right.
Speaker 1 (04:57):
So that's quite interesting that transition. Look up I in
a research anaelist on the investment bankings for twenty seven
years now. I can't even imagine how you how I
came to this number of years, but so I started.
I started in fun in the city in the UK
in nineteen ninety eight. And one of the things I
love about this job is the variety that you deal with,
(05:21):
the variety of people you talk to that you know
you're always learning. And so you've just had that transition
from having worked on three projects then this broad brush
work that you do on sales back to a company
where you've raisly focused on We can talk about some
of the drugs, but obviously the key one car vict,
multiple milemotherapy, et cetera. So I'm assuming that transition was
(05:43):
easy for you because you were in an actual operational role.
Speaker 2 (05:46):
I wouldn't call it easy, Sam, It would be a
you know, serious understandment to say it was easy. But
I can tell you that, even though you know I
had a very stating find career on Wall Street, I
enjoyed my work. I enjoyed talking to so many different companies,
different scientists about new breakthroughs in therapeutics. But still my
(06:10):
heart was always in the industry because I would say,
once a scientist, forever a scientist, right, So, I you know,
one of the biggest regrets when I left the industry
was that Unfortunately, after all those years, right, you know,
toiling in the lab, work on the bench, I was
not associated with an FDA approved the drug. That was
(06:31):
probably my biggest regret when I left the industry back
in two thousand and seven. So it's been always my
dream to say, hey, you know what, I helped develop
a drug, a drug that ultimately benefits patients that was
approved by FDA. So that's probably the biggest reason why
I left Fank America and joined the legend. I mean,
(06:52):
it was not easy decision because how many times do
you want to switch your career in your life, right,
So it's a big risk, so because you never knew
whether this would work out or not. Because unfortunately, after
you know, almost one hundred years right of modern drug discovery,
the odds of a drug candidate succeeding it's always harving
around ten percent. Right, for every ten drug candidates we
(07:16):
brought into first in human studies, one became a drug
right that you know, is oftenly approved by FDA. So
I knew the risk, but still I just had such
a big I guess urge that I really really wanted
to be personally associated with a drug. And I saw
that in CORVICTI that is probably the biggest reason I
(07:37):
took the plunge, So I wouldn't say the transition was easy,
but I take you back, nothing against you, but I
do think that it was a very fulfilling change because
as a CFO about the company, I think the job
is typically divided into two parts. One is what I
(07:57):
call external facing, because you have to raise capital, you
have to work with investment bankers, you have to work
with investors in a byside to bring capital into the
company and then deploy the capital and then also eventually
go public. Right, so that part, I would argue, I
was pretty familiar after working on twelve years on the street. Now.
(08:19):
The other part is internal facing, that is accounting, reporting, budgeting,
tracking spending, and long term planning. So it took some
time for me to get used to it. I was
lucky that, you know, I had a great team. They
helped me get to speed. And also we had a
partner in Johnson Johnson, so I learned a lot from
(08:39):
our partners as well. So I think, you know, take
a little bit of time, but I pretty much would
say that I started to like the job as a CFO,
and then about you know, one on. One and a
half years later, I was put into the CEO. Seed.
Now that is like drinking from the fire holes, I
gotta say, because all of a sudden you'd be in
(09:00):
charge of every aspect of the company, right starting from discovery, research,
to development, to manufacturing and eventually to commercialization. So there's
a lot to learn. But like you said, I think
one of the exciting aspects of analyst on Wall Street
is that you're always learning. So I think I was
well equipped after standing twelve years at analyst because you know,
(09:22):
my mentality is that every day I'm learning, right, So
that helped me transition into the CEO.
Speaker 1 (09:28):
Yeah, so actually this helps us transition, or said great
very nicely into the discussion about Legend. I remember and
correct me if I'm wrong on my dates here, please.
Was it ASCO twenty eighteen when the first data was presented.
Speaker 2 (09:44):
And ASCO twenty seventeen.
Speaker 1 (09:46):
Seventeen, okay, I remember standing at the poster and we'll
talk about what Legend does obviously in a minute, and
everyone was going back here, okay, we don't believe that
data on see our rates or whatever the number was.
Now nobody believed it, and of course then Johnson and
Johnson comes under this deal, so which and then people
(10:08):
thought okay, and nobody believed that's not true. There are
always clearly JJ believed it. So talk to us about
the story, the history of Legend, How did it come about?
And of course you also went into an area where
it was becoming proven slowly cell therapy, engineered cells, T cells,
et cetera. And we get to that, but tell us
(10:29):
a little bit set the background of Legend. How long
has it been around? How did it end up being
there with arguably currently the best CARTI and one of
the best myeloma therapies around.
Speaker 2 (10:43):
Yeah, it was a very great story, I would say. Right. So,
the company was actually founded back in twenty fourteen one
and ten years ago. It was really a spin out
from a former company, a parent company that specializes in
you know, CRO and CDM. More, the company that incubated
Legend was gen Script and Jenscript is a CRO company
(11:05):
which provides a lot of services to corporate clients such
as Big Farmer. So in that process, gen Script developed
expertise in anybody screening, anybody optimization, and even anybody manufacturing.
And then the team of I think it was a
ninth scientist spun out of gen Script in twenty fourteen,
(11:26):
UH to work on therapeutics. Obviously, because of all the
experience in developing and optimizing anybody, they know they want
to work on something that's got anybody on it. But
CARTI was a very early idea back then in twenty fourteen,
So they decided that, hey, you know what, why don't
we work on CARTI because we're not really behind since
(11:48):
it's such a brand new area for new therapeutics. Obviously,
you back then you had two I guess obvious choice
for therapeutic targets. One is CD nineteen. You know, back
then Kim Rayah or you know, yes, Karla was already
being worked on, right, and then the other target was
probably less proven and more interesting, which is BCMA. But
(12:10):
I guess, luckily or maybe because of their scientific insight,
the team decided to focus on BCMA. After about two years,
we came up with a structure called back then it
was code named l car B thirty A M, and
the company started the first impatient studies in twenty sixteen,
(12:31):
and in twenty seventeen at the ASCOM meeting, we presented
for the first time the data from the first thirty
five patients in that trial what we call Legend two,
which is a phase one first in human study, and
like you mentioned, right, it was one hundred percent response rate,
and it was, you know, almost too good to be true.
(12:53):
In fact, I was sitting in that seminar room. I
remember vividly because I followed both Selging and Blue as
an analyst back at the BFA Merrow, So I, you know,
listened to the seminar and obviously it was great data.
Arguably you can say it's better than the BB twenty
one twenty one data from Bloomberg and Selgin. So naturally,
(13:15):
the first thing I did as an analyst was I
want to do some research on Legend. But you know what, Sam,
I couldn't find anything related to this company because it
doesn't have a website when I did the Google search. So,
you know, not surprisingly, right, many any audience, including myself,
we're questioning, okay, is this real because this company it's
(13:37):
such a you know, I guess myth right, do they
even exist? I'm not surprised by the I guess you
could say, the negative reaction from the investors, from companies,
from competitors, from others, right. But the story is that
right in that seminar room, right after the Borrow presentation
(13:58):
was given, a senior clinician from J and J came
to the podium asking our scientists to go to J
ANDJ for a meeting, and they did, right, And that's
when the whole thing started, right, JENJ started diligence, and
about six months later, Legend entered into a global collaboration
(14:20):
agreement with Johnson Johnson. And obviously I'm not here to
discuss all the details about the negotiation and the diligence,
but I can tell you exchange I know, right, Johnathan Johnson.
And also I can tell you Johnson and Johnson team
did very very deep diligous okay, And that impressed the
(14:44):
team at Legend because clearly they were, you're, you know,
really very careful in terms of going into all the details,
finding all the data and the raw data, right, And
that gave I think the Johnson and Johnson team the
conviction to sign such a deal because back then in
twenty seventeen, when we see the deal with J, it
was the largest deal for molecule that was coming out
(15:05):
of China, right, it was three hundred and fifty million
dollars up front payment. Not only that, we're we're also
able to get into an agreement where it was a
fifty to fifty it's not a you know, standard license deal. Instead,
Legend would play a very active role in almost every
aspect of this collaboration. Right, it's a fifty to fifty deal.
(15:25):
We pay fifty percent of all costs including clinical trials, research,
commercialization and facility cap BAX and of course we would
reap also fifty percent of the profit right shared with
J ANDJ. So it was a landmark deal because it
validates designs, validates the clinical data coming from that China
(15:45):
data set, and then put us on the stage.
Speaker 1 (15:49):
Right. So usually that speed of deal and that size
at a time where China was not you know, nowadays
our data suggests ten percent fifteen percent of deals, quite
a lot higher percentage of the big biodollar deals are
coming out of China. But those days, I think you
could count the numbers on the fingers of one or
(16:09):
two hands. So was it a competitive situation or it was?
Speaker 2 (16:15):
Ok it was quite competitive. We had multiple parties in
the process.
Speaker 1 (16:20):
Okay, Well, I think J and J has been one
of the more successful licensing partners that I've looked at
along the years. They've had deals that have fallen apart,
but they've also got deals that have done phenomenally well
for them. And you know, examples are all over the place.
But darz Alex is another one, obviously, and they ended
up being probably the best partner to have for myloma
(16:41):
because they have they have pretty much everything in maloma,
maybe except for small molecules. But right, so, we've talked
about this sufficiently. Now in terms of the history. Let's
talk about specifics now. Just to set the scene here,
I want to make sure that whoever's listening knows what
we're talking about. We're talking about car T cells, chimerica
and degener receptor tea. They are engineered. They are taken
(17:02):
from the patient, they are engineered in the lab and
given back to patients. So there's lots of steps involved.
It's not the most easiest process by any stretch of
the imagination, but it's hyper super active, as you've shown
in the data I've seen so far and others have
been showing. So these engineered cells are manufactured and the
(17:24):
patient has to obviously have a certain amount of time.
I have to wait to get the product back. So
we call this cell therapy. Obviously it's t cell. I'm
calling it that to keep it simple. Where is cell
therapy going, big, big, big picture question.
Speaker 2 (17:37):
Here for you. Yeah, I think we're still in early
days in the stage of devan for tea cell therapy,
because we are all familiar with the story of the
first patient who ever received car te cell therapy, and
that was Emily White hat at Upa right at the medicine.
So that's the first experience and it did not happened
(18:00):
so long ago, right, So I think, you know, for
the naysayers out there, you know who say, you know,
cell therapy will always remain a niche therapy, I actually
respectively disagree because I think we're so early in the stage.
I mean, if you go back, for example, to the
origins of this industry, for the bout deck right about
that was probably you know, in the late nineteen seventies
(18:22):
or in the early nineteen eighties, companies such as Amgene
or Genente were founded. I mean back then, if you
recall many industry you know insiders who say, you know what,
these biologics will never become mensort because it's so costly
to make this the yolde is so low and you
have the price high, and who wants to you know,
get injection? Right? You know, back then, you know, the
(18:43):
whole industry was dominated by oral pills. Right. Well, you know,
look at today, right, look at where we are. The
biggest selling drug today in the world. Kjuda is a
PD one anybody, it's a monoplog anybody. And then you
have you know, coming up, the biggest selling drug will
be a clip onant. It's also injectile right, peptides. So
I think you know, you're right. You mentioned the manufacturing time,
(19:07):
you mentioned the process of collecting cells. But I believe
that science will continue to advance and we will have
all those technical breakthroughs in the future to render cell
therapy very comparative treatment modality. For example, right now we
can actually have a vent to vent time that's shorter
than one month. I mean, yes, it's one month, but
(19:27):
you don't have to wait that long. Now if you
think about the efficacy we can potentially provide to the patients. Right,
we just presented data two months ago in Chicago at
the ASCO meeting because we had a five year minimum
fall up for Party one patients, a third of patients,
a third of late line heavily pre treated patients who
(19:48):
had back then exhausted audio options in the market. Now
they can have a five year treatment free period after
one infusion of correct.
Speaker 1 (19:57):
Let's trillinh Sorry, just so people understand the magnitude of this,
because I'm I'm really excited by you know, there are
three or four cancers now that are this patient population
had a median what six or seven prior lines.
Speaker 2 (20:09):
Six point five lines of private.
Speaker 1 (20:13):
Let's say it again, six point five lines of prior therapy.
I mean, you don't actually get that in many cancers.
So it's great that patients do have access to these lines.
And yet you have people here now after one therapy
who are alive at what rate? Seventy five percent still
alive after five years and they're alive with good is
that right? Just just to raise the.
Speaker 2 (20:33):
Media, survival was just over five years, right, sixty point
seven months actually, Okay, but that's enormous.
Speaker 1 (20:40):
These are patients who would almost certainly been dead by
by So this is this is my AMA is one
of the great success stories in oncology and therapy. So
on that point, this system that we're just describing as
called autologous cell therapy. Right, you also have this idea
of allergenic, so you take seals from anyone, SAM prep them,
(21:04):
and have them ready off the shelf to treat patients with.
But they've had some major issues that you can refer
to if you want to. And you've got this other
idea of in vivo carti therapy so that you actually
deliver almost like a gene therapy, do all the changes
within the patient without having to remove their carties. What's
your thoughts here?
Speaker 2 (21:24):
Is there a.
Speaker 1 (21:24):
Future for allergenic? Is autologs going to get better and
better and better? Is everyone going to end up in
in vivo? Of course the world never works like this,
but just talk to us about your thoughts here.
Speaker 2 (21:34):
Yes, at Legend, we firmly believe that you know, there's
definitely hope here in terms of coming up with off
the shelf, ready to go version of self therpy, and
that could include both modad you just mentioned. SAM one
is allergenic where we take the cells from healthy donors
and then we do the genetic engineering manufacturing in the
(21:56):
lab and then we release those patches. And then the
other one is in vivo, which basically you're injecting the
viral vector that is used to transduce the T cells
in the body to therapeutic car T cells, and you
do honest in a patient's own body. That's why it's
called in vivo. Right. So at legend, we're actually developing
both in the clinic. We have a couple of programs
(22:16):
in the clinic now in phase one stage where we're
developing edited ALPHABETAIT cells. We're also developing gummidela T cells.
So I think the major challenge for allergenic here is
that how do you avoid the rejection by the patient's
own immune system, Because literally you're injecting someone else's cells,
and yes, they can have therapeutic effect, but you know what,
(22:38):
within a few days, typically less than two weeks, let's say,
those cells will be rejected or killed by the patient's
own immune system. Right when that happens. So this is
actually a biggest challenge we have to address. I mean,
I think it's very early, but I think, you know,
based on what we're seeing the clinic, there's definitely hope
that we actually can make that as a reality. Now,
(23:00):
the question is can you develop such an allergenic therapy
that works for majority of patients, right all you can
only see the success in a small minority, So that
is something we're still trying to figure out in a
clinic now. Of course, the most exciting and the most
recent breakthrough is in vivo therapy. Right you have a
few companies in the clinic, including some of our competitors.
(23:22):
You also have seen some major acquisitions, such as AstraZeneca
buying a company called Esselbaltech based in Belgium. They were
conducting a phase one trial with a partner in China.
And then most recently we heard that av spent up
to two point one billion dollars buying Capsin, which is
also now in phase one developing an in vivo cell
(23:45):
therapy for auto immundications. We started our research about twenty
half years ago in Legend, and we're also very pleased
to say that now we have two programs in a
clinic now, both in phase one and we're testing in lymphoma.
So we have those a few patients and that's very early,
but we're encouraged by some of the data to date.
(24:06):
So I do think there's a lot of hope and
enormous potential here. If we can come up with either
elogenic or in vivo therapists, because then all of a sudden,
many many more patients can access this exciting breakthrough.
Speaker 1 (24:20):
Is there a limit on the allergenetic is a little
bit simpler to understand in a comparative basis versustologus. It's
the same process or the same idea in vivo is
of course different because you're trying to deliver a gene.
What are the limitations there? I don't see many BCMA type.
Is there an issue with the complexity of the edits
(24:40):
or intro genes that need to be introduced? See a
lot of the CD nineteen in vivo. What's what's happening there?
Speaker 2 (24:47):
You're right? To date, I believe there's only one in
vivo party, which is the one that was developed by Soobiotech.
They were targeting BCMA, And recently there's a paper me
out I was published on lenset. I think it came
out in June or July. So in that paper they
described four patients, four multi my loma patients were treated
(25:10):
with this in vivo BCMA targeting vector, and in fact
they saw responses including crs and PRS. So I think
it's the first proof in the clinic that you can
actually using the in vivo approach targeting BCMA and treat
the multi my loma. Of course, like I said, this
(25:31):
is the first one and it's the only one that's
been reported in the literature, but I you know, expect
that there will be more and more come into the clinic.
There also will be more reports of this type of
therapy in terms of safety and fats in the literature later.
So I don't think there's a really fundamental difference between
targeting CD nineteen for infoma versus targeting bcm A for
(25:54):
my loma, because both are proven in marketing cartio therapies.
So I think it's just maybe a matter of time
before we know more.
Speaker 1 (26:03):
Yeah, I mean that data is at that two stringent crs,
which is like the best type of CR you can get,
and two prs. Yet seventy five percent from the notes
of seventy five percent grade three crs that should be tunable,
right because you're doing a kick is this something that
you've got a concept of dose? I mean you do
that with car T cells too when you do autologus
(26:24):
or originally, but here you have even more there's better
opportunity here, right for controlling side effects.
Speaker 2 (26:29):
I believe there's a lot we can improve upon that.
So typically what happens is that when you inject a
number of virus particles into the body, you're gett immune response.
Just like you know when patients are in fact with fluid, right,
they don't have all the symptoms. So in this case,
you're injecting you know, a variety of a kind of
virus called lenty virus and then now going to the body.
(26:53):
So you see the first wave of CRS as a
direct immune response to that virus. Now within a few days,
right you saw that from the paper. You know, it
takes about maybe ten days, give or take, and then
the body will start to see the expression of those
cars in the form of cart and then those CARTI
cells will see the energen that will be activated and
(27:15):
will release SAT. Okay, so you see the second wave
of CRS. So I believe the grade three SRS you
just mentioned sam was actually the result of the first wave,
which is the body's immune reaction to the viral particles.
So we believe we can fine tune that by looking
at the dose of the number of various particles inject
and I think you can actually avoid the high graded
(27:36):
crs you saw in the report.
Speaker 1 (27:38):
Okay, so that sounds exciting. Just very quickly to touch
on solid tumors. There's a lot of efforts to develop
what called armored you know. So the just to set
the scene, the difficulty with solid tumors is that liquid
tumors like mylomo, which is not always liquid, but let's
say liquid tumors, you've got a very easy access to
this to the cancer cells through when you apply, whereas
(28:01):
with solid tumors you have literally a solid mass. And
sometimes I'm sure lots of people maybe should close their
ears when I talk about when you take these tumors out,
sometimes they literally are solid, you know, in terms of
their physical characteristics. So that is a problem, right, So,
and people are trying to engineer these cells to create
what we call armored t cells, so it enables you
(28:23):
to get this enable the cells to get into the tumors.
So what is your thinking there? How much effort is
legend spending on solid tumor cardes.
Speaker 2 (28:34):
So first, Sam, let's talk about why solid tumor is
so much harder to treat using CARTI therapty. Right. The
first barrier is what you just mentioned, is to what
we call the physical barrier. When you use cartio therapy
to treat cancers such as lymphoma or my looma, a
lot of those cancer cells are in the blood, right,
So when you inject the car TI therapies into the vat, yes,
(28:56):
you're in immediate contact with the cancer cells and that's
how CARTI can do the job by killing the cells. Right. Now,
for solid tumors such as lung cancer, there's a physical
barrier because once you infuse the CARTI cells, then they
need to travel to the august where the cancer is growing.
So that is a big barrier, right, the physical barrier. Now,
there's also a second barrier, which is that, as we understand,
(29:21):
the solid tumors typically grow in what we call immune
suppressive environment. So the reason why solid tumor can grow
is because they're very smart. Right. The cancer cells trick
our immune system into thinking, oh, this is part of
our own, so that they don't attack it, they don't
kill it. So there's a lot of proteins or a
lot of factors that are what we call immune suppressive.
(29:42):
That is why even if the cart cells eventually are
able to travel to the solid tumor right to the organ,
but because of those suppressive environment the CART cells may
not be able to work effectively. Right, that's a second barrier.
Now the third one which is also very so if
you look at lymphoma or my loma. I mean, let's
(30:03):
use carpectia as one example. Right. The target is BCMA.
It's universally expressed in almost all the my loma cells.
You don't need to even require a certain percentage of
my loma cells to express BCMA because what we found
out is that you don't need to screen patients about that.
In fact, we always see almost perfect response rate. Right.
So that means you know, the cancer is really driven
(30:26):
by that BCM. And now if you kill all the
BCM expressed the cells, you pretty much kill all the
cancer cells. Right now, a solid tumor, for example, lung cancer,
it's always driven by multiple pathways. It's what we call redundancy.
You suppress one pathway, the other one takes over, like
for example, PD one. Right, it's one of the most
(30:47):
effective therapies that are developed to date to treat lung cancer.
But still patients relapse or some page do not respond.
Why because when you suppress PD one, there's other factors
that take over that continue to drive the growth of
the tumor cells. So that is so hard because cart
it's like a precision weapon, right, T cells You can
imagine T cells are missiles in our body. Now CARTI
(31:09):
is basically a weapon, a missile with a precise GPS device,
so we can precisely seek those cancer cells expressing bcm A.
But unfortunately, in the case of solid tumor, there's so
many enggines. There are different pathways that drive the tumor growth.
So it's hard because you know, it's it's very difficult
to developate multi specific car TI to do that. That
(31:33):
is why, for those three reasons, it's difficult to treat
solid tumor. Now, on the other hand, we're not giving
up at legend. We're now in the US side, we
have two I n D open and we have two
phase one trials ongoing. One is Clouding eighteen point two
targeting CARTI we're enrolling and treating patients with lay stage
(31:54):
gastric cancer. The other one is a DL three targeting
CARTI for SMA soil on cancer for which we're partnered
with no artists. We actually publish data at ASCO this year.
And in fact, you do see some efficacies, right, you
do see tumor shrinkage, you do see you know, those
early preliminary signals for efficacy. But I think the key
here is can you get durable response? Right? Because in Carvictie,
(32:18):
what we see is that you get five year survival
from those patients literally dying within months. Right, you get
three year pfs in those Leyland patients. Now in solid tumor.
We're still trying to find out can you get that
level of efficacy? I mean, I must say it's probably
difficult because we have seen many companies developing CARTI for
solid tumor, and so far we have not seen that
(32:41):
level of durability. So that's something you know, we're still
trying to improve.
Speaker 1 (32:46):
Okay, talking about the economics of self therapy, I mean
this is as we talked about earlier on in the conversation,
this is a complex process. It's not a it's a product,
but it's a process. So what lessons have you do
you think you could You've learned about all the different
layers of it. Negotiating with payers because this was a
completely new concept at least perhaps not for Covicti, but
(33:08):
some others that have set the scene controlling manufacturing costs.
What's your thinking about the pricing access to self therapies
and truly moving them to the ultimate goal availability to everybody.
They're not that have access to big academic centers.
Speaker 2 (33:25):
Yeah, so in terms of pricing and access, I think
if you look at Brady how carties are priced, they
are priced in a pretty tight range of let's say
you know about five hundred thousand dollars for treatment costs
right now. The big differentiation is that CARTI is a
(33:45):
one time treatment. In fact, if you look at the
treatment benefit, I could argue that you know, carti in
general are priced very very compatibly. I mean, for example,
we actually published last year a fall up from CARDI four.
So we're either those in patients with just one infusion
of karvicti, all the patients will be continuously dosed with
(34:09):
the cocktail of three different drugs. For example, they might
be those with dollars les, pomlists and daxamothis as a control. Right,
so in natural after a certain time of fall up,
what we found out is that the overall cost is
about I think seven hundred thousand dollars for Karvati treaty
patients in that tw and a half year period. Now,
in the same period the patients in the standard cure control,
(34:32):
the total cost was about one point sixty one point yeah,
one point six million dollars overall. Why because you're using
three drugs for that long right, So in fact Carti
actually provides a significant savings for the system, and that
is why you know, even in Europe, right, Cortis is
actually reimbursed because the government's the agencies for example in
(34:54):
you know countries like UK, they realize there's actually long
term savings here because patients will get only one time
therapy and then they don't require any mental therapy. So
it's a cost of saving for the system. So that
is one thing. Maybe that's not widely known, right people
always look at the price that but you know what,
different from our appills or you know anybody's you don't
(35:16):
need to be continuous those it's a one time therapy.
It's also a huge quality of life improvement for patients
because who wants to be those a day in, there
out and every week uninjectable? Right, So that is one thing.
Now Secondly, I think if you look at the commercial
experience we are having now, it's pretty well reimbursed in
the US and also in some of the European markets
(35:36):
where we've launched convective for. And you know, the payers
always look at the benefit, right. Frequently these days the
payers who look at so called health economic analysis, right,
they look at, okay, what is the one time cost,
and then they look at what is the benefit for
the patients? Right, Like I said, compared to men in
different stand of care, you actually save money. And on
(35:58):
the other hand, we prove super already already to stand
up care in cardio fault for second Land patients in
terms of PFS, in terms of even survival, right, we
saw a survival has a ratio of zero point five five,
which means there's a forty five percent reduction in risks
from death. So clearly I think Cartier as a class
is very economical, right in terms of the healthcare benefits
(36:21):
you're affording to patients and also the system that needs
to be I think understood by both physicians, patients and
as the payers. Now, of course, there's still bottle that
here right in terms of access, because today most of
cartis are being administered in the academic tertiaries hospital setting.
But we're changing that because we have this unique laid
(36:43):
on set CRS profile where the media on set CRS
is typically seven to eight days. Therefore there's not a
really need to hospitalize the patients for the first few
days anyway. This is why in real world in practice,
we're seeing more than half of carvict patients in the
US they actually getting this thirty in the center. But
(37:03):
after a few hours of money during the checked out,
they don't need to stay overnight in that hospital.
Speaker 1 (37:08):
They don't have to stay.
Speaker 2 (37:10):
They can still stay nearby for about maybe up to
two weeks and then they can go home. Actually okay.
Speaker 1 (37:17):
And so one of the interesting things here, of course
is that the a little bit like the GLP ones,
you're kind of manufacturing. You know, you sell as much
as you can make, right, So what's happening there with
the manufacturing capacity? It used to be a bottleneck then,
and J and you guys have spent a lot of
money in Europe in the US. How's that going? Is
(37:37):
that still much of a challenge or you still are
you going to are you able to really just treat
whoever comes along.
Speaker 2 (37:44):
Yeah. I mean, I think we and Gening have come
a long way since twenty twenty two when we launched
corfrect because back then we were severely constrained by our
manufacturing capacity. But as you can tell from the quality
and annual revenue we report it right, actually are making
a lot of progress. In fact, we're on track to
deliver the across the network global capacity of ten thousand
(38:08):
doses per year by end of this year, So that
means entering into twenty twenty six, we and Ginger will
be able to supply the market with at least ten
thousand doses per year for karvating. Now, of course, I
think we continue to improve our capacity because if you
look at the market right, just in the US alone,
we have about one hundred and eighty one hundred and
(38:29):
ninety thousand pages who are diagnosed with a mount from
my looma. They're living with this terrible cancer. So I
think still we have a long way to go, but
I think very soon we'll be able to say we have,
you know, enough compacity to sctisfy all the demand will
get so, like you said, we and Ginger are very
committed to this together. We're spending about a billion dollars
(38:50):
already in terms of CAPEX to you know, estab those
manufacturing facilities and also to improve those and expand our capacity.
In fact, today, as of last quarter, second quarter of
twenty twenty five, Krvecti officially becomes the largest selling carti
product in the market in this category. And you know,
we intend to continue to increase the accessibility so that
(39:12):
more more patients can benefit from carvcti.
Speaker 1 (39:15):
Right Seeing, one of the things that I've got simple maths,
ten thousand patients multiplied by five hundred thousand dollars is
five billion dollars. Now, were both you've been unless im
We don't. It doesn't work like that. Clearly, what percentage
of that capacity is in the US where that price
tag is possible? Number one? Number two. That is the
(39:35):
kind of revenue target. I don't want to call it
target because it's just kind of guidance potential that change
has talked about for twenty thirty and theoretically twenty six
twenty seven, if everyone paid five hundred thousand, you could
get there in twenty six twenty seven. What's how does
(39:56):
this How do those two numbers add up together?
Speaker 2 (40:00):
Yeah? So Right now, the majority of the capacity still
comes from the US. We have the world's largest sealth
are manufacturing facility here in Barton, New Jersey. We're also
contracting with our partner of Artists and we're using their
Maris Plan site in New Jersey to supply carpet as well.
If you look at for example, last quarter is split
(40:22):
right still, like I said about, you know, eighty percent
of our capacity is coming from the US. However, we're
expecting a very significant increase in capacity end of this
year from Europe because right now we have a state
of art two hundred and twenty thousand square foot facility
in tech Clan in the city of Ghent in Belgium
that now has been approved officially for clinical trial material production.
(40:46):
But by end of this year we expect that to
be approved officially by regulatory authorities to start commercial production.
So again, by end of this year or you know,
entering into twenty twenty six, we're going to see a
much bigger capacity coming out of our PM facility. So eventually,
I would say, once our facilities are producing at steady
state rate, you're looking at probably eventually a maybe, I
(41:09):
don't know, forty sixty split. Still the majority of that
wire coming from US, but still the x US market
will become quite significant in the near future. So that's
my answer to our first question. Europe will be a
very important market if you look at some of the
competitors in a CARTI category, and we expect to see
a lot of our revenue coming from Europe as well. Now,
(41:33):
in terms of the pricing, I'm not at liberty to
disclose about all the pricing or reinbursement, but suffice to
say that given the benefit the clinical benefit we have
seen in both late line patients in card one and
now second line in CARTERIO four, I think most payers
really very much understand the benefit corfectly brings to the patients,
(41:53):
and we price according to the benefit. In fact, I
could argue we're pricing you know, we're underpricing compared to
the therapeutic benefit would bring to you patients. But we
e changing are very conscious on this right because we
believe that we need to provide this life saving therapy
to more patients, and that also goes into the consideration
(42:14):
for pricing. Right.
Speaker 1 (42:16):
Just the last question on this thing, I know we've
only got about five ten minutes left what's the hope
at the end of this year? How many what do
you think you'd be able to be No, I know
the ten thousand number, but how many patients do you
think you'll hit by the end of the year.
Speaker 2 (42:32):
It's official policy for our partner, Changine not to provide
product guiders, but I can give you a reference number here, Sam. So,
the seal side analyst has a so called consensus estimate
that predicts the revenue for Corvicti in twenty twenty five
to be about one point a to one point nine
billion dollars, And that is you know what analysts have
(42:55):
given us. Now, I also heard you just mentioned that
our partner gen has previously stated that we firmly believe
carved Ti is a product that's got a peak potential
of five billion dollars at minimum. So you know, I
think we're working very well towards that number, and I
personally am very confident that, yes, eventually there should be
(43:19):
a five billion plus drug. Because I'll give you again,
maybe I should wear my own head of analysts back. Right. So,
when I used to cover Selgia as a sales and analyst,
I remember revenue mid peaked at about thirteen and a
half billion dollars in sales, right, and the computer to
reve livit. I believe Karviti certainly provides more benefit and
also more durable benefit as a one time therapy. So
(43:42):
I think, you know, it's not a far stretch to
think that we can get to you know, less than
half of the peak sales of revenue.
Speaker 3 (43:48):
Right.
Speaker 1 (43:49):
I agree? Why to ask the question the five billion?
Although I think these big drugs and list never quite
imagine them that large, because if you start building those things,
the METARs less, the thing is probably going to end
up at twenty billion, given that they've got a bit
of an irate reprieved. Now, right, let's talk about what's
next for Legend besides correct Yeah, I mean, I think
(44:09):
when do we get data to get us all excited?
Speaker 2 (44:12):
I think, first of all, we'll continue to work hard
in penetration and getting into the community, so we'll get
more and more second land patients to receive CARVICTI. Eventually,
if we can get to about twenty five percent of
that market, that's going to be a number that's much
larger than five billion, because twenty five percent of those
second land patients harbor high risk Saturday and mutations, and
(44:33):
these patients do not respond well to even DRVD, which
is now becoming a good standard for front and therapy.
And once they are relaxed or refraction to that, I
think Carvicti really is the only good choice for those patients.
And that's why we think twenty five percent market penetration
is reasonable. Right, So that's also why we think, you know,
in the future, the five billion plus number is something
(44:54):
we can realize given the data, given the approval, and
also the survival benefit we have already demonstrated from Carvicti.
That's our goal. And then the next one is that
we're also testing Carvicti as a frontline therapy for newly
diagnosed multiple maloma patients. We have a Phase two trial
that's running. We have also two Phase three trials that
are running. In fact, we have closed the enrollment recently
(45:17):
for CARDI six for global enrollment. That is, pitching Carvati
against transplant.
Speaker 1 (45:22):
Had to happen very much looking forward to that data.
Speaker 2 (45:26):
I mean that will probably take a few years too.
Speaker 1 (45:28):
I hope I'm still around right.
Speaker 2 (45:31):
Our ambition, I can tell you from the very beginning
of the collaboration and both the engine legend are perfect aligned,
is that CARVICTI as a cardio therapy is immune therapy.
Therefore it should be used as early as possible when
those T cells from patients are fit, they're young, they're active, right,
So we always had this ambition that krvicti will be
(45:51):
used as a frontlind therapy and you know, and mentions
also to see what kind of efficacy we'll see, right,
So we might start to see some phase two data
maybe you know, in near future, and then we'll get
to the Facebook data maybe also in the next couple
of years from cardio five, right, So that's what's next,
that's fromline and then the next one is beyond cardc TI. Right.
(46:11):
We are investing heavily in solid tumor trials, in allergenic
and now also most recently in vivo therapy. We intend
to keep our leadership in this field of self therapy.
I know there's a lot of naysayers out there in
investment in the world, right, but we firmly believe in
the potential of self therapy because I think that in
cancel care, right, efficacy trumps everything. And I think you
(46:34):
and I both agree that so far CARVICTI is probably
the best efficacy you have ever seen in extreme miloma. Right.
In fact, at the recent the July All That meeting
to discuss bland wrap, right, doctor Paul Richardson from Harvard
Medical School said that in all the second line trials
that been wrong historically in cardio, four was the only
second line trial that showed a statistically significant benefit in
(46:59):
over our survival compared to standard care. So which cancer
patient does not want to live longer? Right? So if
we have that, we have the obligation to bring those
life saving therapy two patients. That is why we'll continue
to do the hard work and we believe that eventually
will come up with off the shelf ready to go
sell therapy.
Speaker 1 (47:19):
The first first hints of data.
Speaker 2 (47:22):
Next year we have some Gamma Dela T program that
is the clinic. Maybe you know, potentially next year we
might have some data from that. Also, we have in
vivo therapy again that's ongoing this year, so maybe again
you know, the psychology.
Speaker 1 (47:38):
We're happy with phase one data just just.
Speaker 2 (47:41):
Yes, can be very much twenty in terms of acacy.
Speaker 1 (47:44):
Yes, exactly right. In the last few minutes that we
have so far, it's been fantastic talking to you legend
obviously started in China, and so I'm interested in your
thoughts about I don't want to talk politics. Is not
a politice conversation I'm interested in. I've been going to
China since two thousand and five as an analyst, and
(48:06):
I've been involved in fundraising from Chinese companies in the
days on the cell side, and I have watched with
amazing interest and all in how quickly and how phenomenally
is China's science evolved. What's the secret source? How do
you think it got there? And how it should the US, which,
(48:29):
as you know, I take party in a conversation called
the biotech hangout with some good friends and we talk
about this regularly. There's a lot of worries in the
US that they're going to we're going to lose out
to China, et cetera. And I think I think science
should be celebrated wherever it happens. Talk to us about this,
what is the secret source? How much should biotech in
the US worry about this?
Speaker 2 (48:50):
Et cetera. First of all, I just came back from
winsiness trip in China last week. In fact, I also
participated in the Everquo Chai Balotech Submit, which was the
first time Womor referenced a very well known boutech aist
who organized such an event. One hundred and twenty institutional
investors and also some farmer BD teams went to Shanghai
(49:13):
to see about fifty local companies right to talk to them.
Wumor himself was in awe, and so were all the
investors I talked to right about the pace of the discovery,
about assignment coming from that sector. I think if you
look at US the bootech right, which I think we
pride ourselves that US is really the birthplace and also
(49:33):
the capital of biotech world right. But I think in
China they're following a similar path because in order first
sectors such as baltech to succeed, you need a very
healthy ecosystem that starts with capital, right. You need enough
venture capital to be able to invest in those risks
taking early stage bototech. Secondly, you need the people, right,
(49:54):
you need all these people with the skill set in
drug discovery and development. Certainly, you need a market, right,
commercial market for the battech sector to thrive. So I
think those three things in the ecosystem, China probably has
done the first two. Right, You have seen a robust investment.
In fact, you know, Hong Kong started to open to
the so called Chapter eighteen eight where they allowed the
(50:16):
pre revenue early stage patacam to go to public just
a five years ago. Yeah, twenty eight is right. So
in the last few years you saw I don't know,
fifty two hundred companies went public in Hong Kong. They
were raising capital and now this year is probably a
renaissance year because a lot of stocks in Hong Kong's
double triple right in value, and you see a lot
of participation from international especially the US and European investors
(50:40):
investing in that because they see the potential, right. So
that's why you have now the necessary capital invested in. Secondly,
I think the people, right, what you see is that
in the last ten to fifteen years, a lot of
very well trend scientists they may you know, grew up
in China, but then they came here for school, they
came to working big farmer and now they're going back.
They were the entrepreneurs to have all the startups, right,
(51:02):
So these people actually know how to discover and develop
a drug, and that's why you're starting to see all
the you know, assets being licensed, even commercial assets, right
that are you know, being marketed already in China, and
then hopefully we'll also come here for market therapy as well.
The third one, I think it remains to be seen
because the truth is right in the whole world, US
(51:23):
has the best market because we have the best pricing
that can support this kind of innovation. I'm not sure
you know when that will materialize in China, to be honest,
even in Europe, right many of my peers are complained
about this because many innovative drugs are not being reimbursed
in country where you're living in your care for it.
So that's a problem. That's why innovation, you know, will
(51:45):
come back to the US because that's where you'll get
paid for. Right. So I do think that the sector
is going be very robust because they have the capital developed,
they have the people, they have the patient to run
trials very efficiently. But eventually they need to come to
the US to tap the market in the US in
order to reward innovation. Now that gets us to the
(52:06):
last question, Right, do we need to fear No? I
don't think so, because we am a firm believer of
capitalist system. That's why you and I. We both worked
in the Wall Street because without capital, how can you
do anything right now, capital needs to be rewarded. But
also for the sector to be competitive, we also need
competition because being in a closed system does not foster efficiency.
(52:28):
And that is why you know, the capital system should
encourage an open competitive system where innovation should compete, right,
because ultimately that benefits the US patients. Why would it
be a bad thing? Why would be not in our
national interest here to benefit from lower costs and shorter
developed plime of new drugs. I mean CORRECTI is a
(52:49):
prime example of that. After we started the collaboration with Jang,
within four years, we were able to bring this life
saving drug in my Lowment to patients in the US,
first manufactured in the US Many US, Yes, we manufact
in the US. We legend employee more than fourteen hundred
team members in the United States. This is our market,
(53:11):
this is our operating country, this is our home right.
So I think it's good for the US to reap
that benefit because whatever discovery that happens in China, we're
reaping the benefit here because we're creating jobs here in
the US. We're developing the US, We're spending in the US.
We're benefiting American patients. So I'm not sure why as
a sector about I should fear that kind of innovation,
(53:34):
because innovation and competition make us stronger. This is why
all the European companies are setting up shops in the US,
because this is where innovation is happening. This is where
innovation is being rewarded.
Speaker 1 (53:45):
You could make the same exact same argument in the
semiconductor field. In the AI field, it is good to
have competition, which is what absolutely as long as you
have no restrictive investment situations or inability to launch your
drugs at the prices that you need to, et cetera.
This has been a fantastic conversation. We're at the hour.
(54:07):
I always promise myself to keep these down to forty
forty five minutes, but when I get interesting people to
talk to, and this has certainly been very interesting, it's
very hard to do that, and there's endless questions here.
Of course, I could have gone deeply deep into the
comparisons of by specific antibodies and try specific etcetcetera, but
we didn't have time for that. I thank you very
(54:28):
much for joining us and taking precious time from you,
and I wish you all the success and look forward
to seeing you, probably at either at IMS I don't
know in Toronto or at ESMO in Berlin. I'm going
to be at both, so look forward to seeing either.
Speaker 2 (54:43):
Thanks very much.
Speaker 3 (55:15):
Pass as bases, uses as bases
Welcome to another episode of Bloomberg Intelligence Vanguards of Healthcare podcast,
where we speak with the leaders at the forefront of
change in the healthcare industry. My name is Sam Fazelli
and I'm a healthcare analyst at Bloomberg Intelligence, the in
house research arm of Bloomberg. I'm thrilled today to welcome
Yeng Huang, who is going to be talking to us
(00:38):
about Legend, the company of which is CEO. It's one
of those great success stories in biotech where they've gone
through what a lot of biotech companies when they start,
it's just a hope in their eyes they have a
product on the market, and not just any product, it's
a product that really has changed the narrative in treatments
(01:01):
of multiple maloma. So I'm really pleased to have being
here with us. Thank you Ying for joining us. The
conversation is going to be divided into three parts. Obviously,
a lot of it's going to be about a legend
and the products and the pipeline. But I wanted to
start offering first to just get a little bit of
your history. You have an interesting history of having been
(01:23):
on the investor side, having been you know, this is
the andlyss side and now the CEO of a company.
Tell us how that transition happened. How did you end
up on Wall Street? Tell us about your story, go
as early as you like, yours, studies, university, what drove you?
This is all very interesting for us.
Speaker 2 (01:41):
Yeah, first of all, thank you Sam, and thank you
to Bloomberg for hosting me and Legend. It's somewhat unconventional
career path for me to go from a scientist to
equity research analyst on Wall Street and then back to
the industry and now being the CEO of Legend. So
I was trained as a scientist. I majored in chemistry
(02:05):
in college. Then I came to the States to pursue
a PhD degree at Columbia University in New York City.
So right after I graduated with a PhD, I joined
a major pharmaceutical company named Sharing Plot, which is now
part of a market company following the acquisition. So I
was there for nine plus years as a medicinal chemist,
(02:27):
working on the bench and leading a group of scientists
working on projects mostly in cardiovascular and CNS disease areas.
Decided to go to business close to the end of
my career at Sharing plot because I developed a pretty
intense interest in the business side. So my original intention
is to go into business development or licensing using my
(02:51):
science expertise and the skill set I acquired from both
Grasco and Work and Sharing. But I took a detour
because that would before financial crisis. It was two thousand
and six, the large majority of my business school classmates
were coming from the banks, and I stumbled into an
opportunity in equity research. So I became a junior analyst
(03:15):
back in two thousand and seven working for about Tech Analyst,
and then I stayed because I found it so intriguing
to be able to talk to so many different companies
with so many different molecues targeting different disease. It was
just eye opening because during my nine year career sharing,
I worked on only three projects, while you know, sitting
(03:37):
in the stead of equity research challengls. Like I said,
all of a sudden, I saw so much science, so
much excitement on developing a breakthrough therapy. So I stayed
and I worked for twelve years on the street. Last
job being at BFA Marriage, where I was a lead
analyst and also managining director, covering the US by tech
(03:58):
sector for the bank. And in twenty nineteen, we had
a common friend between me and the Dance, CEO of
Legend Biotech. We had a conversation about how to bring
a private clinical stage about the companies to the public market.
And then a couple of weeks later, I got a call,
(04:19):
you know, there's an opportunity, there's opening here at the
Legend because they were recruiting a CFO. So I took
the plunge and I joined the company in summer of
twenty nineteen, and then we brought a company in public
in twenty twenty, and then later that year I was
appointed the CEO by the board for Legend. So that's
(04:41):
kind of like how I end up here?
Speaker 1 (04:43):
Did you have to move?
Speaker 2 (04:44):
Not physically because I went to school in New York City.
I worked at a farmer company in New Jersey, so
I've always lived in the state of New Jersey after
graduation from school, so I did not have to move physically,
you know, right.
Speaker 1 (04:57):
So that's quite interesting that transition. Look up I in
a research anaelist on the investment bankings for twenty seven
years now. I can't even imagine how you how I
came to this number of years, but so I started.
I started in fun in the city in the UK
in nineteen ninety eight. And one of the things I
love about this job is the variety that you deal with,
(05:21):
the variety of people you talk to that you know
you're always learning. And so you've just had that transition
from having worked on three projects then this broad brush
work that you do on sales back to a company
where you've raisly focused on We can talk about some
of the drugs, but obviously the key one car vict,
multiple milemotherapy, et cetera. So I'm assuming that transition was
(05:43):
easy for you because you were in an actual operational role.
Speaker 2 (05:46):
I wouldn't call it easy, Sam, It would be a
you know, serious understandment to say it was easy. But
I can tell you that, even though you know I
had a very stating find career on Wall Street, I
enjoyed my work. I enjoyed talking to so many different companies,
different scientists about new breakthroughs in therapeutics. But still my
(06:10):
heart was always in the industry because I would say,
once a scientist, forever a scientist, right, So, I you know,
one of the biggest regrets when I left the industry
was that Unfortunately, after all those years, right, you know,
toiling in the lab, work on the bench, I was
not associated with an FDA approved the drug. That was
(06:31):
probably my biggest regret when I left the industry back
in two thousand and seven. So it's been always my
dream to say, hey, you know what, I helped develop
a drug, a drug that ultimately benefits patients that was
approved by FDA. So that's probably the biggest reason why
I left Fank America and joined the legend. I mean,
(06:52):
it was not easy decision because how many times do
you want to switch your career in your life, right,
So it's a big risk, so because you never knew
whether this would work out or not. Because unfortunately, after
you know, almost one hundred years right of modern drug discovery,
the odds of a drug candidate succeeding it's always harving
around ten percent. Right, for every ten drug candidates we
(07:16):
brought into first in human studies, one became a drug
right that you know, is oftenly approved by FDA. So
I knew the risk, but still I just had such
a big I guess urge that I really really wanted
to be personally associated with a drug. And I saw
that in CORVICTI that is probably the biggest reason I
(07:37):
took the plunge, So I wouldn't say the transition was easy,
but I take you back, nothing against you, but I
do think that it was a very fulfilling change because
as a CFO about the company, I think the job
is typically divided into two parts. One is what I
(07:57):
call external facing, because you have to raise capital, you
have to work with investment bankers, you have to work
with investors in a byside to bring capital into the
company and then deploy the capital and then also eventually
go public. Right, so that part, I would argue, I
was pretty familiar after working on twelve years on the street. Now.
(08:19):
The other part is internal facing, that is accounting, reporting, budgeting,
tracking spending, and long term planning. So it took some
time for me to get used to it. I was
lucky that, you know, I had a great team. They
helped me get to speed. And also we had a
partner in Johnson Johnson, so I learned a lot from
(08:39):
our partners as well. So I think, you know, take
a little bit of time, but I pretty much would
say that I started to like the job as a CFO,
and then about you know, one on. One and a
half years later, I was put into the CEO. Seed.
Now that is like drinking from the fire holes, I
gotta say, because all of a sudden you'd be in
(09:00):
charge of every aspect of the company, right starting from discovery, research,
to development, to manufacturing and eventually to commercialization. So there's
a lot to learn. But like you said, I think
one of the exciting aspects of analyst on Wall Street
is that you're always learning. So I think I was
well equipped after standing twelve years at analyst because you know,
(09:22):
my mentality is that every day I'm learning, right, So
that helped me transition into the CEO.
Speaker 1 (09:28):
Yeah, so actually this helps us transition, or said great
very nicely into the discussion about Legend. I remember and
correct me if I'm wrong on my dates here, please.
Was it ASCO twenty eighteen when the first data was presented.
Speaker 2 (09:44):
And ASCO twenty seventeen.
Speaker 1 (09:46):
Seventeen, okay, I remember standing at the poster and we'll
talk about what Legend does obviously in a minute, and
everyone was going back here, okay, we don't believe that
data on see our rates or whatever the number was.
Now nobody believed it, and of course then Johnson and
Johnson comes under this deal, so which and then people
(10:08):
thought okay, and nobody believed that's not true. There are
always clearly JJ believed it. So talk to us about
the story, the history of Legend, How did it come about?
And of course you also went into an area where
it was becoming proven slowly cell therapy, engineered cells, T cells,
et cetera. And we get to that, but tell us
(10:29):
a little bit set the background of Legend. How long
has it been around? How did it end up being
there with arguably currently the best CARTI and one of
the best myeloma therapies around.
Speaker 2 (10:43):
Yeah, it was a very great story, I would say. Right. So,
the company was actually founded back in twenty fourteen one
and ten years ago. It was really a spin out
from a former company, a parent company that specializes in
you know, CRO and CDM. More, the company that incubated
Legend was gen Script and Jenscript is a CRO company
(11:05):
which provides a lot of services to corporate clients such
as Big Farmer. So in that process, gen Script developed
expertise in anybody screening, anybody optimization, and even anybody manufacturing.
And then the team of I think it was a
ninth scientist spun out of gen Script in twenty fourteen,
(11:26):
UH to work on therapeutics. Obviously, because of all the
experience in developing and optimizing anybody, they know they want
to work on something that's got anybody on it. But
CARTI was a very early idea back then in twenty fourteen,
So they decided that, hey, you know what, why don't
we work on CARTI because we're not really behind since
(11:48):
it's such a brand new area for new therapeutics. Obviously,
you back then you had two I guess obvious choice
for therapeutic targets. One is CD nineteen. You know, back
then Kim Rayah or you know, yes, Karla was already
being worked on, right, and then the other target was
probably less proven and more interesting, which is BCMA. But
(12:10):
I guess, luckily or maybe because of their scientific insight,
the team decided to focus on BCMA. After about two years,
we came up with a structure called back then it
was code named l car B thirty A M, and
the company started the first impatient studies in twenty sixteen,
(12:31):
and in twenty seventeen at the ASCOM meeting, we presented
for the first time the data from the first thirty
five patients in that trial what we call Legend two,
which is a phase one first in human study, and
like you mentioned, right, it was one hundred percent response rate,
and it was, you know, almost too good to be true.
(12:53):
In fact, I was sitting in that seminar room. I
remember vividly because I followed both Selging and Blue as
an analyst back at the BFA Merrow, So I, you know,
listened to the seminar and obviously it was great data.
Arguably you can say it's better than the BB twenty
one twenty one data from Bloomberg and Selgin. So naturally,
(13:15):
the first thing I did as an analyst was I
want to do some research on Legend. But you know what, Sam,
I couldn't find anything related to this company because it
doesn't have a website when I did the Google search. So,
you know, not surprisingly, right, many any audience, including myself,
we're questioning, okay, is this real because this company it's
(13:37):
such a you know, I guess myth right, do they
even exist? I'm not surprised by the I guess you
could say, the negative reaction from the investors, from companies,
from competitors, from others, right. But the story is that
right in that seminar room, right after the Borrow presentation
(13:58):
was given, a senior clinician from J and J came
to the podium asking our scientists to go to J
ANDJ for a meeting, and they did, right, And that's
when the whole thing started, right, JENJ started diligence, and
about six months later, Legend entered into a global collaboration
(14:20):
agreement with Johnson Johnson. And obviously I'm not here to
discuss all the details about the negotiation and the diligence,
but I can tell you exchange I know, right, Johnathan Johnson.
And also I can tell you Johnson and Johnson team
did very very deep diligous okay, And that impressed the
(14:44):
team at Legend because clearly they were, you're, you know,
really very careful in terms of going into all the details,
finding all the data and the raw data, right, And
that gave I think the Johnson and Johnson team the
conviction to sign such a deal because back then in
twenty seventeen, when we see the deal with J, it
was the largest deal for molecule that was coming out
(15:05):
of China, right, it was three hundred and fifty million
dollars up front payment. Not only that, we're we're also
able to get into an agreement where it was a
fifty to fifty it's not a you know, standard license deal. Instead,
Legend would play a very active role in almost every
aspect of this collaboration. Right, it's a fifty to fifty deal.
(15:25):
We pay fifty percent of all costs including clinical trials, research,
commercialization and facility cap BAX and of course we would
reap also fifty percent of the profit right shared with
J ANDJ. So it was a landmark deal because it
validates designs, validates the clinical data coming from that China
(15:45):
data set, and then put us on the stage.
Speaker 1 (15:49):
Right. So usually that speed of deal and that size
at a time where China was not you know, nowadays
our data suggests ten percent fifteen percent of deals, quite
a lot higher percentage of the big biodollar deals are
coming out of China. But those days, I think you
could count the numbers on the fingers of one or
(16:09):
two hands. So was it a competitive situation or it was?
Speaker 2 (16:15):
Ok it was quite competitive. We had multiple parties in
the process.
Speaker 1 (16:20):
Okay, Well, I think J and J has been one
of the more successful licensing partners that I've looked at
along the years. They've had deals that have fallen apart,
but they've also got deals that have done phenomenally well
for them. And you know, examples are all over the place.
But darz Alex is another one, obviously, and they ended
up being probably the best partner to have for myloma
(16:41):
because they have they have pretty much everything in maloma,
maybe except for small molecules. But right, so, we've talked
about this sufficiently. Now in terms of the history. Let's
talk about specifics now. Just to set the scene here,
I want to make sure that whoever's listening knows what
we're talking about. We're talking about car T cells, chimerica
and degener receptor tea. They are engineered. They are taken
(17:02):
from the patient, they are engineered in the lab and
given back to patients. So there's lots of steps involved.
It's not the most easiest process by any stretch of
the imagination, but it's hyper super active, as you've shown
in the data I've seen so far and others have
been showing. So these engineered cells are manufactured and the
(17:24):
patient has to obviously have a certain amount of time.
I have to wait to get the product back. So
we call this cell therapy. Obviously it's t cell. I'm
calling it that to keep it simple. Where is cell
therapy going, big, big, big picture question.
Speaker 2 (17:37):
Here for you. Yeah, I think we're still in early
days in the stage of devan for tea cell therapy,
because we are all familiar with the story of the
first patient who ever received car te cell therapy, and
that was Emily White hat at Upa right at the medicine.
So that's the first experience and it did not happened
(18:00):
so long ago, right, So I think, you know, for
the naysayers out there, you know who say, you know,
cell therapy will always remain a niche therapy, I actually
respectively disagree because I think we're so early in the stage.
I mean, if you go back, for example, to the
origins of this industry, for the bout deck right about
that was probably you know, in the late nineteen seventies
(18:22):
or in the early nineteen eighties, companies such as Amgene
or Genente were founded. I mean back then, if you
recall many industry you know insiders who say, you know what,
these biologics will never become mensort because it's so costly
to make this the yolde is so low and you
have the price high, and who wants to you know,
get injection? Right? You know, back then, you know, the
(18:43):
whole industry was dominated by oral pills. Right. Well, you know,
look at today, right, look at where we are. The
biggest selling drug today in the world. Kjuda is a
PD one anybody, it's a monoplog anybody. And then you
have you know, coming up, the biggest selling drug will
be a clip onant. It's also injectile right, peptides. So
I think you know, you're right. You mentioned the manufacturing time,
(19:07):
you mentioned the process of collecting cells. But I believe
that science will continue to advance and we will have
all those technical breakthroughs in the future to render cell
therapy very comparative treatment modality. For example, right now we
can actually have a vent to vent time that's shorter
than one month. I mean, yes, it's one month, but
(19:27):
you don't have to wait that long. Now if you
think about the efficacy we can potentially provide to the patients. Right,
we just presented data two months ago in Chicago at
the ASCO meeting because we had a five year minimum
fall up for Party one patients, a third of patients,
a third of late line heavily pre treated patients who
(19:48):
had back then exhausted audio options in the market. Now
they can have a five year treatment free period after
one infusion of correct.
Speaker 1 (19:57):
Let's trillinh Sorry, just so people understand the magnitude of this,
because I'm I'm really excited by you know, there are
three or four cancers now that are this patient population
had a median what six or seven prior lines.
Speaker 2 (20:09):
Six point five lines of private.
Speaker 1 (20:13):
Let's say it again, six point five lines of prior therapy.
I mean, you don't actually get that in many cancers.
So it's great that patients do have access to these lines.
And yet you have people here now after one therapy
who are alive at what rate? Seventy five percent still
alive after five years and they're alive with good is
that right? Just just to raise the.
Speaker 2 (20:33):
Media, survival was just over five years, right, sixty point
seven months actually, Okay, but that's enormous.
Speaker 1 (20:40):
These are patients who would almost certainly been dead by
by So this is this is my AMA is one
of the great success stories in oncology and therapy. So
on that point, this system that we're just describing as
called autologous cell therapy. Right, you also have this idea
of allergenic, so you take seals from anyone, SAM prep them,
(21:04):
and have them ready off the shelf to treat patients with.
But they've had some major issues that you can refer
to if you want to. And you've got this other
idea of in vivo carti therapy so that you actually
deliver almost like a gene therapy, do all the changes
within the patient without having to remove their carties. What's
your thoughts here?
Speaker 2 (21:24):
Is there a.
Speaker 1 (21:24):
Future for allergenic? Is autologs going to get better and
better and better? Is everyone going to end up in
in vivo? Of course the world never works like this,
but just talk to us about your thoughts here.
Speaker 2 (21:34):
Yes, at Legend, we firmly believe that you know, there's
definitely hope here in terms of coming up with off
the shelf, ready to go version of self therpy, and
that could include both modad you just mentioned. SAM one
is allergenic where we take the cells from healthy donors
and then we do the genetic engineering manufacturing in the
(21:56):
lab and then we release those patches. And then the
other one is in vivo, which basically you're injecting the
viral vector that is used to transduce the T cells
in the body to therapeutic car T cells, and you
do honest in a patient's own body. That's why it's
called in vivo. Right. So at legend, we're actually developing
both in the clinic. We have a couple of programs
(22:16):
in the clinic now in phase one stage where we're
developing edited ALPHABETAIT cells. We're also developing gummidela T cells.
So I think the major challenge for allergenic here is
that how do you avoid the rejection by the patient's
own immune system, Because literally you're injecting someone else's cells,
and yes, they can have therapeutic effect, but you know what,
(22:38):
within a few days, typically less than two weeks, let's say,
those cells will be rejected or killed by the patient's
own immune system. Right when that happens. So this is
actually a biggest challenge we have to address. I mean,
I think it's very early, but I think, you know,
based on what we're seeing the clinic, there's definitely hope
that we actually can make that as a reality. Now,
(23:00):
the question is can you develop such an allergenic therapy
that works for majority of patients, right all you can
only see the success in a small minority, So that
is something we're still trying to figure out in a
clinic now. Of course, the most exciting and the most
recent breakthrough is in vivo therapy. Right you have a
few companies in the clinic, including some of our competitors.
(23:22):
You also have seen some major acquisitions, such as AstraZeneca
buying a company called Esselbaltech based in Belgium. They were
conducting a phase one trial with a partner in China.
And then most recently we heard that av spent up
to two point one billion dollars buying Capsin, which is
also now in phase one developing an in vivo cell
(23:45):
therapy for auto immundications. We started our research about twenty
half years ago in Legend, and we're also very pleased
to say that now we have two programs in a
clinic now, both in phase one and we're testing in lymphoma.
So we have those a few patients and that's very early,
but we're encouraged by some of the data to date.
(24:06):
So I do think there's a lot of hope and
enormous potential here. If we can come up with either
elogenic or in vivo therapists, because then all of a sudden,
many many more patients can access this exciting breakthrough.
Speaker 1 (24:20):
Is there a limit on the allergenetic is a little
bit simpler to understand in a comparative basis versustologus. It's
the same process or the same idea in vivo is
of course different because you're trying to deliver a gene.
What are the limitations there? I don't see many BCMA type.
Is there an issue with the complexity of the edits
(24:40):
or intro genes that need to be introduced? See a
lot of the CD nineteen in vivo. What's what's happening there?
Speaker 2 (24:47):
You're right? To date, I believe there's only one in
vivo party, which is the one that was developed by Soobiotech.
They were targeting BCMA, And recently there's a paper me
out I was published on lenset. I think it came
out in June or July. So in that paper they
described four patients, four multi my loma patients were treated
(25:10):
with this in vivo BCMA targeting vector, and in fact
they saw responses including crs and PRS. So I think
it's the first proof in the clinic that you can
actually using the in vivo approach targeting BCMA and treat
the multi my loma. Of course, like I said, this
(25:31):
is the first one and it's the only one that's
been reported in the literature, but I you know, expect
that there will be more and more come into the clinic.
There also will be more reports of this type of
therapy in terms of safety and fats in the literature later.
So I don't think there's a really fundamental difference between
targeting CD nineteen for infoma versus targeting bcm A for
(25:54):
my loma, because both are proven in marketing cartio therapies.
So I think it's just maybe a matter of time
before we know more.
Speaker 1 (26:03):
Yeah, I mean that data is at that two stringent crs,
which is like the best type of CR you can get,
and two prs. Yet seventy five percent from the notes
of seventy five percent grade three crs that should be tunable,
right because you're doing a kick is this something that
you've got a concept of dose? I mean you do
that with car T cells too when you do autologus
(26:24):
or originally, but here you have even more there's better
opportunity here, right for controlling side effects.
Speaker 2 (26:29):
I believe there's a lot we can improve upon that.
So typically what happens is that when you inject a
number of virus particles into the body, you're gett immune response.
Just like you know when patients are in fact with fluid, right,
they don't have all the symptoms. So in this case,
you're injecting you know, a variety of a kind of
virus called lenty virus and then now going to the body.
(26:53):
So you see the first wave of CRS as a
direct immune response to that virus. Now within a few days,
right you saw that from the paper. You know, it
takes about maybe ten days, give or take, and then
the body will start to see the expression of those
cars in the form of cart and then those CARTI
cells will see the energen that will be activated and
(27:15):
will release SAT. Okay, so you see the second wave
of CRS. So I believe the grade three SRS you
just mentioned sam was actually the result of the first wave,
which is the body's immune reaction to the viral particles.
So we believe we can fine tune that by looking
at the dose of the number of various particles inject
and I think you can actually avoid the high graded
(27:36):
crs you saw in the report.
Speaker 1 (27:38):
Okay, so that sounds exciting. Just very quickly to touch
on solid tumors. There's a lot of efforts to develop
what called armored you know. So the just to set
the scene, the difficulty with solid tumors is that liquid
tumors like mylomo, which is not always liquid, but let's
say liquid tumors, you've got a very easy access to
this to the cancer cells through when you apply, whereas
(28:01):
with solid tumors you have literally a solid mass. And
sometimes I'm sure lots of people maybe should close their
ears when I talk about when you take these tumors out,
sometimes they literally are solid, you know, in terms of
their physical characteristics. So that is a problem, right, So,
and people are trying to engineer these cells to create
what we call armored t cells, so it enables you
(28:23):
to get this enable the cells to get into the tumors.
So what is your thinking there? How much effort is
legend spending on solid tumor cardes.
Speaker 2 (28:34):
So first, Sam, let's talk about why solid tumor is
so much harder to treat using CARTI therapty. Right. The
first barrier is what you just mentioned, is to what
we call the physical barrier. When you use cartio therapy
to treat cancers such as lymphoma or my looma, a
lot of those cancer cells are in the blood, right,
So when you inject the car TI therapies into the vat, yes,
(28:56):
you're in immediate contact with the cancer cells and that's
how CARTI can do the job by killing the cells. Right. Now,
for solid tumors such as lung cancer, there's a physical
barrier because once you infuse the CARTI cells, then they
need to travel to the august where the cancer is growing.
So that is a big barrier, right, the physical barrier. Now,
there's also a second barrier, which is that, as we understand,
(29:21):
the solid tumors typically grow in what we call immune
suppressive environment. So the reason why solid tumor can grow
is because they're very smart. Right. The cancer cells trick
our immune system into thinking, oh, this is part of
our own, so that they don't attack it, they don't
kill it. So there's a lot of proteins or a
lot of factors that are what we call immune suppressive.
(29:42):
That is why even if the cart cells eventually are
able to travel to the solid tumor right to the organ,
but because of those suppressive environment the CART cells may
not be able to work effectively. Right, that's a second barrier.
Now the third one which is also very so if
you look at lymphoma or my loma. I mean, let's
(30:03):
use carpectia as one example. Right. The target is BCMA.
It's universally expressed in almost all the my loma cells.
You don't need to even require a certain percentage of
my loma cells to express BCMA because what we found
out is that you don't need to screen patients about that.
In fact, we always see almost perfect response rate. Right.
So that means you know, the cancer is really driven
(30:26):
by that BCM. And now if you kill all the
BCM expressed the cells, you pretty much kill all the
cancer cells. Right now, a solid tumor, for example, lung cancer,
it's always driven by multiple pathways. It's what we call redundancy.
You suppress one pathway, the other one takes over, like
for example, PD one. Right, it's one of the most
(30:47):
effective therapies that are developed to date to treat lung cancer.
But still patients relapse or some page do not respond.
Why because when you suppress PD one, there's other factors
that take over that continue to drive the growth of
the tumor cells. So that is so hard because cart
it's like a precision weapon, right, T cells You can
imagine T cells are missiles in our body. Now CARTI
(31:09):
is basically a weapon, a missile with a precise GPS device,
so we can precisely seek those cancer cells expressing bcm A.
But unfortunately, in the case of solid tumor, there's so
many enggines. There are different pathways that drive the tumor growth.
So it's hard because you know, it's it's very difficult
to developate multi specific car TI to do that. That
(31:33):
is why, for those three reasons, it's difficult to treat
solid tumor. Now, on the other hand, we're not giving
up at legend. We're now in the US side, we
have two I n D open and we have two
phase one trials ongoing. One is Clouding eighteen point two
targeting CARTI we're enrolling and treating patients with lay stage
(31:54):
gastric cancer. The other one is a DL three targeting
CARTI for SMA soil on cancer for which we're partnered
with no artists. We actually publish data at ASCO this year.
And in fact, you do see some efficacies, right, you
do see tumor shrinkage, you do see you know, those
early preliminary signals for efficacy. But I think the key
here is can you get durable response? Right? Because in Carvictie,
(32:18):
what we see is that you get five year survival
from those patients literally dying within months. Right, you get
three year pfs in those Leyland patients. Now in solid tumor.
We're still trying to find out can you get that
level of efficacy? I mean, I must say it's probably
difficult because we have seen many companies developing CARTI for
solid tumor, and so far we have not seen that
(32:41):
level of durability. So that's something you know, we're still
trying to improve.
Speaker 1 (32:46):
Okay, talking about the economics of self therapy, I mean
this is as we talked about earlier on in the conversation,
this is a complex process. It's not a it's a product,
but it's a process. So what lessons have you do
you think you could You've learned about all the different
layers of it. Negotiating with payers because this was a
completely new concept at least perhaps not for Covicti, but
(33:08):
some others that have set the scene controlling manufacturing costs.
What's your thinking about the pricing access to self therapies
and truly moving them to the ultimate goal availability to everybody.
They're not that have access to big academic centers.
Speaker 2 (33:25):
Yeah, so in terms of pricing and access, I think
if you look at Brady how carties are priced, they
are priced in a pretty tight range of let's say
you know about five hundred thousand dollars for treatment costs
right now. The big differentiation is that CARTI is a
(33:45):
one time treatment. In fact, if you look at the
treatment benefit, I could argue that you know, carti in
general are priced very very compatibly. I mean, for example,
we actually published last year a fall up from CARDI four.
So we're either those in patients with just one infusion
of karvicti, all the patients will be continuously dosed with
(34:09):
the cocktail of three different drugs. For example, they might
be those with dollars les, pomlists and daxamothis as a control. Right,
so in natural after a certain time of fall up,
what we found out is that the overall cost is
about I think seven hundred thousand dollars for Karvati treaty
patients in that tw and a half year period. Now,
in the same period the patients in the standard cure control,
(34:32):
the total cost was about one point sixty one point yeah,
one point six million dollars overall. Why because you're using
three drugs for that long right, So in fact Carti
actually provides a significant savings for the system, and that
is why you know, even in Europe, right, Cortis is
actually reimbursed because the government's the agencies for example in
(34:54):
you know countries like UK, they realize there's actually long
term savings here because patients will get only one time
therapy and then they don't require any mental therapy. So
it's a cost of saving for the system. So that
is one thing. Maybe that's not widely known, right people
always look at the price that but you know what,
different from our appills or you know anybody's you don't
(35:16):
need to be continuous those it's a one time therapy.
It's also a huge quality of life improvement for patients
because who wants to be those a day in, there
out and every week uninjectable? Right, So that is one thing.
Now Secondly, I think if you look at the commercial
experience we are having now, it's pretty well reimbursed in
the US and also in some of the European markets
(35:36):
where we've launched convective for. And you know, the payers
always look at the benefit, right. Frequently these days the
payers who look at so called health economic analysis, right,
they look at, okay, what is the one time cost,
and then they look at what is the benefit for
the patients? Right, Like I said, compared to men in
different stand of care, you actually save money. And on
(35:58):
the other hand, we prove super already already to stand
up care in cardio fault for second Land patients in
terms of PFS, in terms of even survival, right, we
saw a survival has a ratio of zero point five five,
which means there's a forty five percent reduction in risks
from death. So clearly I think Cartier as a class
is very economical, right in terms of the healthcare benefits
(36:21):
you're affording to patients and also the system that needs
to be I think understood by both physicians, patients and
as the payers. Now, of course, there's still bottle that
here right in terms of access, because today most of
cartis are being administered in the academic tertiaries hospital setting.
But we're changing that because we have this unique laid
(36:43):
on set CRS profile where the media on set CRS
is typically seven to eight days. Therefore there's not a
really need to hospitalize the patients for the first few
days anyway. This is why in real world in practice,
we're seeing more than half of carvict patients in the
US they actually getting this thirty in the center. But
(37:03):
after a few hours of money during the checked out,
they don't need to stay overnight in that hospital.
Speaker 1 (37:08):
They don't have to stay.
Speaker 2 (37:10):
They can still stay nearby for about maybe up to
two weeks and then they can go home. Actually okay.
Speaker 1 (37:17):
And so one of the interesting things here, of course
is that the a little bit like the GLP ones,
you're kind of manufacturing. You know, you sell as much
as you can make, right, So what's happening there with
the manufacturing capacity? It used to be a bottleneck then,
and J and you guys have spent a lot of
money in Europe in the US. How's that going? Is
(37:37):
that still much of a challenge or you still are
you going to are you able to really just treat
whoever comes along.
Speaker 2 (37:44):
Yeah. I mean, I think we and Gening have come
a long way since twenty twenty two when we launched
corfrect because back then we were severely constrained by our
manufacturing capacity. But as you can tell from the quality
and annual revenue we report it right, actually are making
a lot of progress. In fact, we're on track to
deliver the across the network global capacity of ten thousand
(38:08):
doses per year by end of this year, So that
means entering into twenty twenty six, we and Ginger will
be able to supply the market with at least ten
thousand doses per year for karvating. Now, of course, I
think we continue to improve our capacity because if you
look at the market right, just in the US alone,
we have about one hundred and eighty one hundred and
(38:29):
ninety thousand pages who are diagnosed with a mount from
my looma. They're living with this terrible cancer. So I
think still we have a long way to go, but
I think very soon we'll be able to say we have,
you know, enough compacity to sctisfy all the demand will
get so, like you said, we and Ginger are very
committed to this together. We're spending about a billion dollars
(38:50):
already in terms of CAPEX to you know, estab those
manufacturing facilities and also to improve those and expand our capacity.
In fact, today, as of last quarter, second quarter of
twenty twenty five, Krvecti officially becomes the largest selling carti
product in the market in this category. And you know,
we intend to continue to increase the accessibility so that
(39:12):
more more patients can benefit from carvcti.
Speaker 1 (39:15):
Right Seeing, one of the things that I've got simple maths,
ten thousand patients multiplied by five hundred thousand dollars is
five billion dollars. Now, were both you've been unless im
We don't. It doesn't work like that. Clearly, what percentage
of that capacity is in the US where that price
tag is possible? Number one? Number two. That is the
(39:35):
kind of revenue target. I don't want to call it
target because it's just kind of guidance potential that change
has talked about for twenty thirty and theoretically twenty six
twenty seven, if everyone paid five hundred thousand, you could
get there in twenty six twenty seven. What's how does
(39:56):
this How do those two numbers add up together?
Speaker 2 (40:00):
Yeah? So Right now, the majority of the capacity still
comes from the US. We have the world's largest sealth
are manufacturing facility here in Barton, New Jersey. We're also
contracting with our partner of Artists and we're using their
Maris Plan site in New Jersey to supply carpet as well.
If you look at for example, last quarter is split
(40:22):
right still, like I said about, you know, eighty percent
of our capacity is coming from the US. However, we're
expecting a very significant increase in capacity end of this
year from Europe because right now we have a state
of art two hundred and twenty thousand square foot facility
in tech Clan in the city of Ghent in Belgium
that now has been approved officially for clinical trial material production.
(40:46):
But by end of this year we expect that to
be approved officially by regulatory authorities to start commercial production.
So again, by end of this year or you know,
entering into twenty twenty six, we're going to see a
much bigger capacity coming out of our PM facility. So eventually,
I would say, once our facilities are producing at steady
state rate, you're looking at probably eventually a maybe, I
(41:09):
don't know, forty sixty split. Still the majority of that
wire coming from US, but still the x US market
will become quite significant in the near future. So that's
my answer to our first question. Europe will be a
very important market if you look at some of the
competitors in a CARTI category, and we expect to see
a lot of our revenue coming from Europe as well. Now,
(41:33):
in terms of the pricing, I'm not at liberty to
disclose about all the pricing or reinbursement, but suffice to
say that given the benefit the clinical benefit we have
seen in both late line patients in card one and
now second line in CARTERIO four, I think most payers
really very much understand the benefit corfectly brings to the patients,
(41:53):
and we price according to the benefit. In fact, I
could argue we're pricing you know, we're underpricing compared to
the therapeutic benefit would bring to you patients. But we
e changing are very conscious on this right because we
believe that we need to provide this life saving therapy
to more patients, and that also goes into the consideration
(42:14):
for pricing. Right.
Speaker 1 (42:16):
Just the last question on this thing, I know we've
only got about five ten minutes left what's the hope
at the end of this year? How many what do
you think you'd be able to be No, I know
the ten thousand number, but how many patients do you
think you'll hit by the end of the year.
Speaker 2 (42:32):
It's official policy for our partner, Changine not to provide
product guiders, but I can give you a reference number here, Sam. So,
the seal side analyst has a so called consensus estimate
that predicts the revenue for Corvicti in twenty twenty five
to be about one point a to one point nine
billion dollars, And that is you know what analysts have
(42:55):
given us. Now, I also heard you just mentioned that
our partner gen has previously stated that we firmly believe
carved Ti is a product that's got a peak potential
of five billion dollars at minimum. So you know, I
think we're working very well towards that number, and I
personally am very confident that, yes, eventually there should be
(43:19):
a five billion plus drug. Because I'll give you again,
maybe I should wear my own head of analysts back. Right. So,
when I used to cover Selgia as a sales and analyst,
I remember revenue mid peaked at about thirteen and a
half billion dollars in sales, right, and the computer to
reve livit. I believe Karviti certainly provides more benefit and
also more durable benefit as a one time therapy. So
(43:42):
I think, you know, it's not a far stretch to
think that we can get to you know, less than
half of the peak sales of revenue.
Speaker 3 (43:48):
Right.
Speaker 1 (43:49):
I agree? Why to ask the question the five billion?
Although I think these big drugs and list never quite
imagine them that large, because if you start building those things,
the METARs less, the thing is probably going to end
up at twenty billion, given that they've got a bit
of an irate reprieved. Now, right, let's talk about what's
next for Legend besides correct Yeah, I mean, I think
(44:09):
when do we get data to get us all excited?
Speaker 2 (44:12):
I think, first of all, we'll continue to work hard
in penetration and getting into the community, so we'll get
more and more second land patients to receive CARVICTI. Eventually,
if we can get to about twenty five percent of
that market, that's going to be a number that's much
larger than five billion, because twenty five percent of those
second land patients harbor high risk Saturday and mutations, and
(44:33):
these patients do not respond well to even DRVD, which
is now becoming a good standard for front and therapy.
And once they are relaxed or refraction to that, I
think Carvicti really is the only good choice for those patients.
And that's why we think twenty five percent market penetration
is reasonable. Right, So that's also why we think, you know,
in the future, the five billion plus number is something
(44:54):
we can realize given the data, given the approval, and
also the survival benefit we have already demonstrated from Carvicti.
That's our goal. And then the next one is that
we're also testing Carvicti as a frontline therapy for newly
diagnosed multiple maloma patients. We have a Phase two trial
that's running. We have also two Phase three trials that
are running. In fact, we have closed the enrollment recently
(45:17):
for CARDI six for global enrollment. That is, pitching Carvati
against transplant.
Speaker 1 (45:22):
Had to happen very much looking forward to that data.
Speaker 2 (45:26):
I mean that will probably take a few years too.
Speaker 1 (45:28):
I hope I'm still around right.
Speaker 2 (45:31):
Our ambition, I can tell you from the very beginning
of the collaboration and both the engine legend are perfect aligned,
is that CARVICTI as a cardio therapy is immune therapy.
Therefore it should be used as early as possible when
those T cells from patients are fit, they're young, they're active, right,
So we always had this ambition that krvicti will be
(45:51):
used as a frontlind therapy and you know, and mentions
also to see what kind of efficacy we'll see, right,
So we might start to see some phase two data
maybe you know, in near future, and then we'll get
to the Facebook data maybe also in the next couple
of years from cardio five, right, So that's what's next,
that's fromline and then the next one is beyond cardc TI. Right.
(46:11):
We are investing heavily in solid tumor trials, in allergenic
and now also most recently in vivo therapy. We intend
to keep our leadership in this field of self therapy.
I know there's a lot of naysayers out there in
investment in the world, right, but we firmly believe in
the potential of self therapy because I think that in
cancel care, right, efficacy trumps everything. And I think you
(46:34):
and I both agree that so far CARVICTI is probably
the best efficacy you have ever seen in extreme miloma. Right.
In fact, at the recent the July All That meeting
to discuss bland wrap, right, doctor Paul Richardson from Harvard
Medical School said that in all the second line trials
that been wrong historically in cardio, four was the only
second line trial that showed a statistically significant benefit in
(46:59):
over our survival compared to standard care. So which cancer
patient does not want to live longer? Right? So if
we have that, we have the obligation to bring those
life saving therapy two patients. That is why we'll continue
to do the hard work and we believe that eventually
will come up with off the shelf ready to go
sell therapy.
Speaker 1 (47:19):
The first first hints of data.
Speaker 2 (47:22):
Next year we have some Gamma Dela T program that
is the clinic. Maybe you know, potentially next year we
might have some data from that. Also, we have in
vivo therapy again that's ongoing this year, so maybe again
you know, the psychology.
Speaker 1 (47:38):
We're happy with phase one data just just.
Speaker 2 (47:41):
Yes, can be very much twenty in terms of acacy.
Speaker 1 (47:44):
Yes, exactly right. In the last few minutes that we
have so far, it's been fantastic talking to you legend
obviously started in China, and so I'm interested in your
thoughts about I don't want to talk politics. Is not
a politice conversation I'm interested in. I've been going to
China since two thousand and five as an analyst, and
(48:06):
I've been involved in fundraising from Chinese companies in the
days on the cell side, and I have watched with
amazing interest and all in how quickly and how phenomenally
is China's science evolved. What's the secret source? How do
you think it got there? And how it should the US, which,
(48:29):
as you know, I take party in a conversation called
the biotech hangout with some good friends and we talk
about this regularly. There's a lot of worries in the
US that they're going to we're going to lose out
to China, et cetera. And I think I think science
should be celebrated wherever it happens. Talk to us about this,
what is the secret source? How much should biotech in
the US worry about this?
Speaker 2 (48:50):
Et cetera. First of all, I just came back from
winsiness trip in China last week. In fact, I also
participated in the Everquo Chai Balotech Submit, which was the
first time Womor referenced a very well known boutech aist
who organized such an event. One hundred and twenty institutional
investors and also some farmer BD teams went to Shanghai
(49:13):
to see about fifty local companies right to talk to them.
Wumor himself was in awe, and so were all the
investors I talked to right about the pace of the discovery,
about assignment coming from that sector. I think if you
look at US the bootech right, which I think we
pride ourselves that US is really the birthplace and also
(49:33):
the capital of biotech world right. But I think in
China they're following a similar path because in order first
sectors such as baltech to succeed, you need a very
healthy ecosystem that starts with capital, right. You need enough
venture capital to be able to invest in those risks
taking early stage bototech. Secondly, you need the people, right,
(49:54):
you need all these people with the skill set in
drug discovery and development. Certainly, you need a market, right,
commercial market for the battech sector to thrive. So I
think those three things in the ecosystem, China probably has
done the first two. Right, You have seen a robust investment.
In fact, you know, Hong Kong started to open to
the so called Chapter eighteen eight where they allowed the
(50:16):
pre revenue early stage patacam to go to public just
a five years ago. Yeah, twenty eight is right. So
in the last few years you saw I don't know,
fifty two hundred companies went public in Hong Kong. They
were raising capital and now this year is probably a
renaissance year because a lot of stocks in Hong Kong's
double triple right in value, and you see a lot
of participation from international especially the US and European investors
(50:40):
investing in that because they see the potential, right. So
that's why you have now the necessary capital invested in. Secondly,
I think the people, right, what you see is that
in the last ten to fifteen years, a lot of
very well trend scientists they may you know, grew up
in China, but then they came here for school, they
came to working big farmer and now they're going back.
They were the entrepreneurs to have all the startups, right,
(51:02):
So these people actually know how to discover and develop
a drug, and that's why you're starting to see all
the you know, assets being licensed, even commercial assets, right
that are you know, being marketed already in China, and
then hopefully we'll also come here for market therapy as well.
The third one, I think it remains to be seen
because the truth is right in the whole world, US
(51:23):
has the best market because we have the best pricing
that can support this kind of innovation. I'm not sure
you know when that will materialize in China, to be honest,
even in Europe, right many of my peers are complained
about this because many innovative drugs are not being reimbursed
in country where you're living in your care for it.
So that's a problem. That's why innovation, you know, will
(51:45):
come back to the US because that's where you'll get
paid for. Right. So I do think that the sector
is going be very robust because they have the capital developed,
they have the people, they have the patient to run
trials very efficiently. But eventually they need to come to
the US to tap the market in the US in
order to reward innovation. Now that gets us to the
(52:06):
last question, Right, do we need to fear No? I
don't think so, because we am a firm believer of
capitalist system. That's why you and I. We both worked
in the Wall Street because without capital, how can you
do anything right now, capital needs to be rewarded. But
also for the sector to be competitive, we also need
competition because being in a closed system does not foster efficiency.
(52:28):
And that is why you know, the capital system should
encourage an open competitive system where innovation should compete, right,
because ultimately that benefits the US patients. Why would it
be a bad thing? Why would be not in our
national interest here to benefit from lower costs and shorter
developed plime of new drugs. I mean CORRECTI is a
(52:49):
prime example of that. After we started the collaboration with Jang,
within four years, we were able to bring this life
saving drug in my Lowment to patients in the US,
first manufactured in the US Many US, Yes, we manufact
in the US. We legend employee more than fourteen hundred
team members in the United States. This is our market,
(53:11):
this is our operating country, this is our home right.
So I think it's good for the US to reap
that benefit because whatever discovery that happens in China, we're
reaping the benefit here because we're creating jobs here in
the US. We're developing the US, We're spending in the US.
We're benefiting American patients. So I'm not sure why as
a sector about I should fear that kind of innovation,
(53:34):
because innovation and competition make us stronger. This is why
all the European companies are setting up shops in the US,
because this is where innovation is happening. This is where
innovation is being rewarded.
Speaker 1 (53:45):
You could make the same exact same argument in the
semiconductor field. In the AI field, it is good to
have competition, which is what absolutely as long as you
have no restrictive investment situations or inability to launch your
drugs at the prices that you need to, et cetera.
This has been a fantastic conversation. We're at the hour.
(54:07):
I always promise myself to keep these down to forty
forty five minutes, but when I get interesting people to
talk to, and this has certainly been very interesting, it's
very hard to do that, and there's endless questions here.
Of course, I could have gone deeply deep into the
comparisons of by specific antibodies and try specific etcetcetera, but
we didn't have time for that. I thank you very
(54:28):
much for joining us and taking precious time from you,
and I wish you all the success and look forward
to seeing you, probably at either at IMS I don't
know in Toronto or at ESMO in Berlin. I'm going
to be at both, so look forward to seeing either.
Speaker 2 (54:43):
Thanks very much.
Speaker 3 (55:15):
Pass as bases, uses as bases
Host
Jonathan Palmer
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