June 12, 2025 • 57 mins
“The thing that I worry about more than loss of exclusivity is this term that I introduced at the AACR meeting -- loss of relevancy" says Susan Galbraith, EVP of Oncology R&D at AstraZeneca. In this episode, Galbraith and David Fredrickson, EVP of Oncology Business Unit, join Bloomberg Intelligence analyst Sam Fazeli fresh from ASCO to discuss how AstraZeneca is navigating an increasingly complex oncology landscape. From a legacy in small molecules to a bold push into areas ranging from cell therapy to antibody-drug conjugates, they explain how the company aims to sustain growth and relevance. The discussion also covers new trial designs, biomarker-driven strategies, and why innovation, not exclusivity, is the true metric of success.
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Episode Transcript
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Speaker 1 (00:13):
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.
I'm a senior pharmer analyst at Bloomberg Intelligence, the in
house research arm of Bloomberg. I am thrilled to be
talking to Susan Goldbraid and David Frederickson from AstraZeneca today
(00:37):
with our focus on oncology hot on the heels of
the ASCO Convention, which is always a bit of a
whirlwind when it happens and you come out the other end.
Speaker 2 (00:49):
Trying to organize your thoughts.
Speaker 1 (00:51):
So this is an ideal time for us to be
doing this, and I'm really really delighted to have both of.
Speaker 2 (00:58):
You on the call now.
Speaker 1 (01:01):
Just to introduce, I doubt there's anybody out there who
doesn't know who you are. So Susan Goldbraid is Executive
Vice President of Oncology Hematology R and D at Astrosenica,
and Dave Fredrickson is Executive vice President of Oncology Hematology
Business at Astroseneka.
Speaker 2 (01:18):
So we have the.
Speaker 1 (01:19):
Two leaders here which quite clearly have amazing teams because
of the continuous progress that the company is making. I'm
going to start off, if I may, by just talking
some big picture strategy here, susan Astro. Seneca's legacy has
been in small molecules, right, I mean, you're the leader
(01:40):
in lung cancer. Is you off our positive lung cancer
with Tagriso. But now the company's focused more on novel modalities.
Speaker 2 (01:47):
What's changed? What has shifted here? Or are you still
looking into small molecules?
Speaker 1 (01:53):
Is this dare I say it an effect from the
IRA small molecule penalty pill penalty? Do you want to
just talk us through that a little bit?
Speaker 3 (02:02):
Yeah? So, as you say, we have got a good
chat record of delivering medicines that are from the small
molecule background. But you know, increasingly the range of options
that are available through more sophisticated putt in engineering, development
of modalities like te sell engages and the development of
(02:23):
modealities like antibody drug conjugates means as a range of
opportunity for medicines in those spaces as well. So it's
more that the opportunity set has grown in things that
are larger than small molecules. But of course, with the
Swena six data that were presented at ASCO. You know,
it's not that we're backing away from small molecules in
any way, shape or form, and we have other drugs
(02:45):
like zoriprib, which is part one selective molecule in phase
three is another example. But there are lots of exciting
new models that are coming through, as I've mentioned, and
I think in terms of the thinking about the impact
of the IRA and tail end of the life cycle curve,
if you like, the thing that I worry about more
(03:06):
than loss of exclusivity or that is this term that
I introduced at the ACM meeting of loss of relevancy,
that the pace of innovation is increasing so much now
that actually there's an opportunity for disruption of things that
have already been established during their life cycle rather than
at the end of their life cycle. So that's what
(03:27):
I think we have to keep an eye on, and
that's why we're investing, you know, not just in the
programs that we need to deliver for approvals in the
next four or five years, but also in those modalities
that will deliver beyond that time period. And that's why,
for example, continued investment into the cell therapy area including
the recent acquisition of Isobiotech to access in vivo cell
(03:52):
therapy modality for example. That's very important as well, because
you know, I can see that that has potential to
be a disruptive force. So that's the philosophy really, rather
than one about the current view on time period until
you start having negotiation from the IRA.
Speaker 2 (04:11):
Well, I love that.
Speaker 1 (04:12):
I love that phrase when I heard it first time
you were on that panel, when you mentioned it at
the PREACR meeting. The problem for us analyst is that
loss of exclusivity is relatively easy. You see a date,
you assume it's going to go. You maybe add six
months for some kind of extra exclusivity. Then you do
a generic erosion lots of relevance. That's a much harder
(04:33):
tea to calculate and workout. But so thank you very
much for doing that and making our lives even harder
now talking about lots of relevance, of course, it.
Speaker 2 (04:41):
Cuts both ways.
Speaker 1 (04:42):
Some other company might change the relevance of your compound,
and you might do the same to others. So you've
got a whole bunch of readouts coming out this year
over the next.
Speaker 2 (04:50):
Twelve months, So we're going to go exactly.
Speaker 1 (04:51):
Twelve months to next asco what are the ones, what
are the hot ones that if you could do that,
I'm not asking you to pick your drugs, I'm asking
you to pick your particular readouts here.
Speaker 2 (05:02):
That you're that you're looking forward to. Anything is going
to make a difference to our next question.
Speaker 3 (05:07):
Yeah, sure, we'll just extend the timeline a little bit
to the end of next year so that we're not
giving more specific guidance than is normal for us at
this point in a year. But of course there's a
lot of interest in the evans A study in first
line nonsmal cell on cancer. This is the combination of
datchaway our chrope two based ADC with infimsy r PDO
(05:30):
or antibody in the first line setting a non SMaL
cell lung cancer. So my view is that I guess
perhaps disproportionate focus, but beyond that, actually, it was so
pleased to see the Niagara study be there last year
that we presented the planary at ESMO, and we now
have the Vulgar study which looks at the combination of
(05:51):
infimsy and importuma prodota in that perioperative setting in bladder cancer.
So that's an exciting study. We have another more in
her to read out. We've already announced positive top line
results for Destiny breast eleven in the new agudant setting,
but we looking forward to the results of Destiny BREASTO five,
(06:13):
which is in the post near agulant setting in early
stage her two positive breast cancer. Of course, extending from
the Serena six data that we had ADASCO, this is
the potential for the Serena four data in the broader
first line population of your positive advanced breast cancer. And
then the next day you c that people aren't yet
(06:35):
paying as much attention to, which is you know a
Zedden nine oh one which now has a name son
citemeg for doton, which we call sonny V. That's in
the Cloita GASTRICO one study in second line plus gastric cancer.
Speaker 2 (06:52):
What's the mechanism there.
Speaker 3 (06:54):
That's a it's targeting chlaudine eighteen point two and it's
got an MMAE based payload on that dragon. Again, we
had encouraging response rate, endurability of response that was seen
and we've taken that into the light line. But there
will be you know, other investments that you'll see coming
with building on that molecule, we have the Emerald three
(07:14):
study for infemsy and habita cellular cancer, and then in addition,
in the EADI far mutant subset of lung cancer, we've
got the Chropian line fifteen study, which is a combination
of data away and ossimertanib in that second line, post
Surgen Tki in the first line.
Speaker 1 (07:34):
Yeah, we've been I've been listening and thinking and talking
to as many physicians as I can about this increasingly
complex world of EGOFAR mutiated lung cancer. Because you had
physicians had one choice until quite recently, and now suddenly
flora to Myriposa mariposa too, and then you get all
the second line options, maybe even PD one VEG who
(07:57):
knows right, So, but I'm going to turn to Dave.
Now you've listed a series of readouts. You've also got
an incremental approximately thirty billion, let's say thirty five billion
or so, whatever the exact number is to get to
your eighty billion dollar target. Can you just Dave took
us through how much of that you think could come
(08:17):
from oncology, and then how many of these readouts are
particularly important for that target?
Speaker 3 (08:25):
Thanks?
Speaker 4 (08:25):
Sam Well when we reported out earnings at the end
of last year, and indeed, when we take a look
at first quarter, about forty percent of total company or
enterprise revenues come from oncology. So certainly, as Susan and
I look out towards twenty thirty and beyond, we expect
oncology to be at least at that level of composition
(08:49):
of sales. So I think that, you know, we should
look forward to and expect, just in rough measures, that
perhaps maybe half of the growth that we want to
get to from where we are today to this eighty
billion ambition that we set out for twenty thirty would
come from oncology. And I think that there's two really
key drivers of that, and we saw both of those
(09:10):
at play at this most recent ASCO. One is that
we've been working very diligently to maximize the clinical development
plans for our existing launched assets. Two examples of those
obviously we saw INFINSI with the Matterhorn data at ASCO,
where we have an opportunity to bring in FINSI into
(09:32):
a perioperative curative intent gastric esophageal junction cancer setting. INFINSI
is one of our fastest growing inline medicines that we
have within oncology. That is coming on the heels of
a number of first in class, best in class studies
that we've been investing behind. And then you also saw
(09:53):
on Her too, as Susan mentioned too before with the
Destiny Bresto nine data, again a multi blockbuster indication spansion
opportunity on two medicines that we already have in hand.
So that's the big first piece, which is maximizing those
clinical development plans. The second is obviously launching new medicines.
AstraZeneca's laid out a objective to contribute twenty new medicines
(10:16):
by twenty thirty in order to get to that eighty
billion dollar ambition, and then to have a sustainable pipeline
in order to drive business thereafter. And hopefully we will
be able to see the approval of camas Estrant on
the back of data from Serena six. Also, certainly breakthrough
therapy designation being a good indicator that the FDA sees
(10:39):
these as important data as well. And we've got multiple
five billion dollar plus potential new assets that we see
in the pipeline. Camas Estron is one. Also, are IOBI specifics,
which I'm sure we'll talk a little bit more about later,
but Revalgustamig, which is PD one legit by specific Volustomig,
(11:02):
which is a PD one CTLA four serup rib small molecule.
Back to your previous question, in the park space, really
building off of Limparza and our pioneering work there, and
then in the hematology space, serav Atamig, which is a
CD nineteen CD three T cell engager that we're taking
(11:22):
into multiple hematologic settings, and AZD zero one two zero,
which is our car T therapy, which we'll launch into
multiple miloma first, but where we've got ambitions to expand
beyond that. So we've got seven assets that are yet
to launch that we think have multi blockbuster potential to
(11:44):
drive us not just to twenty thirty, but really importantly
sustainably in the next decade.
Speaker 1 (11:50):
Thanks for that, Dave. One of the issues, of course,
you're facing is that some of these are going into
really crowded spaces. Do you feel that they're SACD nineteen
City three or the Mylomo asset. Do you feel that
you think you're going to have sufficient differentiation to be
able to get take indrois or are they just a foothold,
(12:11):
And then there's of course the I and I applications
of a whole bunch of these inflammation and imienology.
Speaker 4 (12:17):
I mean, at the most important strategic level, we go
through about every two weeks investments into our Phase three
studies through what we call portfolio Review Committee. And one
of the key areas of focus when we make capital
allocations and we think about clinical trials is do we
have the opportunity to be first in class or best
(12:38):
in class? Back to Susan's point about loss of relevance,
there's nothing worse than launching irrelevant. That's instant loss of relevance.
And so we've been working very diligently to ensure that
we've got some best in class competitive intelligence capabilities. We
work to make sure that we are bringing the most
(13:00):
innovative studies that go into what we call white space,
space that's not occupied by other competitors. And we also
work to execute as best we can to be first
in places that are deeply competitive. I would say beyond
those dimensions, certainly, we think that we've got opportunities to
(13:20):
create advantage through a couple of core areas that we
work on. One of them is we think that we've
got differentiated patient identification approaches, so certainly how we approach
computational pathology things like Serena six, which was using an
opportunity to identify patients and incorporating that precision medicine approach
(13:41):
into our studies as one. And combination approaches is another
area for advantage where we see opportunities to combine multiple
assets within the Astrazenica portfolio to be able to do
things more quickly and indeed perhaps combinations before competitions able
to engage in the same sets of studies and just.
Speaker 3 (14:01):
Entering us specifically about the serivatimik, the CD nineteen, CD
three and Azada one two oh or CD nineteen b
CMA carties. So let me just give you some examples
that illustrate the points that Dave was saying. So Savatamig
was designed with lower affinity CD three to have a
better therapeutic index in terms of cytocin release syndrome, but
(14:24):
because it also target CD nineteen, which has a broader
range of expression across B cells, has a potential for
differentiation from some of the CD twenty based decil engages
that are currently there and Actually, we've presented some data
at ASCO in the fuse large B soulen theoma, which
as you go up through the target dose range, you know,
(14:46):
shows improvements in a complete response rates that really I
think are very competitive with what you've seen with other
molecules out there, and we'll be presenting some data EHA
later this week in a the bustic leukemia with also
I think very competitive al rates. So the design of
the molecule was selected to try and provide that differentiation.
(15:09):
And then again the dual car targeting that we've got
with as a one two plus the fastcar manufacturing process
gives it a really nice profile overall. You know, we
presented some data at ASH last year, small numbers admittedly,
but in newly diagnosed multiple myeloma with patients that are
(15:31):
high risk. You know, we saw one hundred percent CR
rate and ninety five two hundred percent MRD negativity rate.
So I think it can be very competitive, even though
as you rightly point out, that field is a very
competitive one.
Speaker 1 (15:46):
Let me let me just move on to a couple
more questions. I'm now realizing that we needed two hours
for this, but never mind. So you've had a bunch
of recent term readouts that you're not only improving or
potentially improving standard of care by drug replacements, substitutions, et cetera,
as is the usual case, but really focused on even
(16:06):
changing the practice. So SERENA six testing for ESR one
emersions right, advans are using QCs, You're really at the
edge of that marriage of diagnostics and.
Speaker 2 (16:20):
Therapy.
Speaker 1 (16:21):
And so I wanted to just get a feel for
what's your thinking behind this approach and did the drugs
just lead you here or is there a broader process
going This is how we're going to differentiate and help
patients better.
Speaker 3 (16:34):
Yeah, well, I think there's a background philosophy which you've
seen not just in these two programs, but really you
know with the approvals with them PASA and with SRISA,
which is that you know, understanding the right patients to
treat within each patient population is a fundamental part of
that differentiation process. So we always work on that and
(16:56):
at an early stage, and we have also not had
not just had success in doing that within the R
and D space, but partnership with Dave's team, you know,
working for some years before the potential launch to make
sure that we have the ability to then deliver it
into the commercial space and drive that uptake. You know,
you forget now, but looking back, having a next gen
(17:20):
sequencing based ctDNA test for example, wasn't obvious at the
time that we started doing that within the clinic called trials,
and so I think that's analogous to the use of
quantity to continue scoring, which is based on AI machine
learning ability with computational pathology. We acquired a company, Definians
(17:42):
several years ago, which was originally trying to look at
biomarkers for IO mechanisms of prediction. When we then did
the deal with Diretyusankia for access to and her too
and then subsequently for data d x T now de way,
you know, it was obvious to me that we were
(18:04):
going to need biomarkers for these what are you know,
self surface directed targeted therapies in order to optimize the
benefit risk, and so we worked with that computational pathology
team to see if there are ways that we could
better identify those and understand it. So that was a
you know that QCs biomark has been five years in
the in the development, so it absolutely is not just
(18:27):
because we saw what we saw entropy and Longo one.
It was a philosophy from the time of the partnership
initiating that this is something that we're going to need
an investment behind it at risk to do that. And
I think with the Serena six data as well, this
is a is going into a white space, as Dave said,
which is it was a way for us to accelerate
(18:50):
into that first line setting and get experience in a
place where we thought you're most likely to be able
to show the improved benefit risk. In this case, we
do think that chemists astro will also work in the
broader wild type patient population, but this gave us an
opportunity to get early into the first line and so
(19:11):
it was very much, you know, an opportunistic approach for
chemis astron.
Speaker 1 (19:18):
I mean, that's eminently sensible, but unfortunately our world doesn't
just follow sensible stuff, right, so we have a you know,
I want to move to Dave here quickly. You think
about QCs, the NMR and es R one testing for
Serena six. These eminently sensible, but how confident are you
(19:39):
that payers and physicians and we heard the questions when
you presented the Serenus six data with regards to the
number of tests or that have to how often do
we test patients to know that they are the s
R one is emerging, et cetera.
Speaker 2 (19:53):
How confident are you that you'd.
Speaker 1 (19:55):
Be able to get them on the same path on
this journey, not just in the US, but let's face it,
Europe and China are maybe I don't know, easier and
more difficult.
Speaker 4 (20:07):
Well, I have a great deal of confidence Sam that
when clinical data are compelling, that we have worked together
in the markets with stakeholders that we are operating in
to be able to create access to these important biomarkers.
And really most of the portfolio that we've launched for
(20:30):
the last ten years has some type of biomarker associated
with it. So in that regard, there's certainly a deep
amount of experience that we have I think a couple
other important pieces.
Speaker 5 (20:41):
You know, a lot of times.
Speaker 4 (20:44):
Biomarkers are relevant for research purposes, but when they become
relevant for making treatment and clinical decisions, that's when we
start to see that the sense of urgency really increases. Also,
the cost will only go down from here. We know
that that's true across other areas that we've looked at
(21:04):
and why is that, Well, it's because different parts of
the globe and different companies look for ways to create
resource appropriate solutions to deliver decentralized approaches to diagnostics. There's
partners that we work with like Sophia Genetics who's working
to expand access to tissue and liquid panels through their
(21:30):
work in collaboration with memorial slum kettering even examples and
this is a bit of a tangent, if you will,
but it's relevant when you take a look at the
work that cure Ai does in order to be able
to take lung cancer scans or X rays and turn
them into the equivalent of CT scans in terms of
the value that comes out of from for lung cancer screening.
(21:52):
We see so many different opportunities where technology is creating
resource appropriate, decentralized approaches to being able to deliver these
kinds of precision medicine approach.
Speaker 5 (22:03):
So there will be a learning curve.
Speaker 4 (22:05):
We are going to absolutely need to work together in
all of the markets that we launch in in order
to ensure that there is supply of ESR one mutation
testing and QCs in order to meet the demand that
we think that these studies either have with Serena six
or could with a von Zar demonstrate right. But I
(22:29):
also have confidence that it's a path that we understand
how to move ourselves down.
Speaker 2 (22:34):
This actually etc.
Speaker 1 (22:35):
Is very well into their next question for you, Dave,
In terms of oncology treatment in ten years time, I
think one way to think about is look back ten years.
Speaker 2 (22:42):
It's not exactly ten years.
Speaker 1 (22:44):
That Tagrisa has been in the market, but EGFR patient
came in with Lunkhan said they had one choice, physician
made a decision, patient went home. Now you have to
perhaps think about them from a brain mets sitting, ecoc sitting, etc. Right,
how many what's the burden of disease when it comes
to choosing? How do you see this in tenuous time?
More disease segmentation, more cures one hopes, more diagnostics by markers.
Speaker 2 (23:09):
Where are we? What else is there to think about it?
Speaker 1 (23:11):
And that makes your life and your cost higher. Although
you just said that these things get cheaper as time goes.
Speaker 4 (23:17):
On, Well, yes, I see more of those things, and
after I offer a response, it certainly welcome Susan in
on this.
Speaker 5 (23:25):
You know it's interesting.
Speaker 4 (23:25):
Eleven years ago Susan and I had an opportunity to
launch Limparsa together, and the first global launch for that
was in the United States, actually in Denver, Colorado, where
we came together. And we've had an opportunity to watch
many trends that were really just kind of sparkles in
(23:45):
our eye and imagination of the future really begin to
take hold and really progress along. And I think we'll
see more and more of that as we look to
the future. So we are absolutely moving beyond a one
size fits all a part So yes, more precision medicine.
We are working hard to move into earlier settings of
(24:07):
disease where we can drive to cures. What are some
of the specific things that we're doing. Novel ADCs are
replacing backbone chemotherapies. I think when you take a look
at discussions that were happening in twenty twenty five at ASCO,
it's not about will ADC's deliver on their promise, but
how do we incorporate them into treatment? How do we
(24:27):
think about sequences, sequencing, how can we think about best
ways of personalizing for the patients who can benefit. Secondly,
we talked about this before, but next generation immunotherapy agents
will absolutely represent to raise the bar to deliver better
responses to io than what we've seen with checkpoint inhibitors.
(24:47):
To date, checkpoint inheritors have made an enormous amount of progress,
but too few patients respond and they don't respond long
enough in all of the instances. There's a great opportunity
to do even more to enhance and rebuild the immune system.
Speaker 5 (25:00):
There'll be advances to that point.
Speaker 6 (25:01):
In cell therapy and T cell engagers.
Speaker 4 (25:04):
Certainly, cell therapy has represented an enormous step forward in
terms of breathtaking responses in terms of some of the
complete responses that we see in studies, yet it's been
limited largely to hematologic malignancies. The opportunity to bring that
into solid tumors and actually outside of oncology into the
autoimmune space is incredibly exciting. And then also can we
(25:27):
use T cell engagers to rebuild the immune system in
a way that perhaps is not nearly as supply chain
constrained as what we get through some of the autocar approaches.
The power of combinations is a fourth major trend, and
we talked about this before, but we think combinations will
transform survival and cancer, and in particular, the last piece
(25:49):
fifth is early intervention. By moving earlier, we see the
greatest opportunity to be able to drive towards what hopefully
are long term, durable responses, which.
Speaker 6 (25:59):
We have the opportunity energy to describe as cures.
Speaker 4 (26:01):
So yes, in the future, more cures, more segments, more personalized,
more combinations. And the way that we're able to make
sure that that doesn't just result in so much complexity
is I think that we've got to really embrace technology
that's going to allow for us to be able to
(26:22):
have physicians be aided in their clinical decision making process.
There's work that we need to do on moving from
individual diagnostic testing to multiplexing. There's a number of things
that we do to try to capitalize on scale that
we have in tumor types like breast cancer, lung cancer,
GI cancers, to be able to find ways to ensure
(26:45):
that we're able to maximize each of these individual indications
and assets and opportunities for patients and do it in
a way that is taking advantage of a cost base
and an intellectual capability base that's already built up within
these areas.
Speaker 2 (27:00):
You know, Dave, that sounds like AI to me. If
you could put AI sticks.
Speaker 1 (27:04):
Now that's a phrase that's overused and in some cases underused.
I don't know what we'll we'll see how that all
pans out, Susan, did you want to make a comment
on this.
Speaker 3 (27:13):
Well, now, obviously, I think one thing to think about
with these combinations that we're thinking is not that everything
gets dosed on top of everything, but you can actually
create kind of regimens. I still think that you're going
to need kind of debulking regimens, if you like, for
which I think combinations of either the ADCs or already
conjugates together with some of the new immunotherapy agents you know,
(27:36):
can help to do that. And you see evidence for
that in some of the emerging neo adjutant data we presented,
for example at the Near Coast to study at ASCO,
which is an ADC datid HD plus io and with
that with which was infimasy. With that combination, we kind
of doubled the paths and doubled the major pathologic response
(27:58):
rate compared with what you got with ioplus chemo and
the A G and trial, if you like. So there's
an illustration of the fact that you can do that.
But still, you know, even if you've got into that setting,
some of the patients will relapse from that, so you
probably still need some consolidation. And this is the place
(28:19):
where I think if you can get people into a
patsy R or MRD negative state even after to say
first line metastatic disease, that's the place where I really
think that the cell therapy is most likely to then
show the long term benefit. So you know that it's
not just about everything on top of one another. It's
(28:41):
the you know, induction and consolidation maybe the way to
think about it.
Speaker 1 (28:45):
I think you've answered two or three questions all in
one go there. If you wanted to just pick one
or two moas that you have in your pipeline be
in phase one, that's that you would put in the
category of a twinkle in your eye that in teniest
time we've got to look back and.
Speaker 2 (29:00):
Say, wow, what are you hopeful for?
Speaker 1 (29:02):
Of course, you know we all know how biology and
especially in oncology makes us humble, but that's absolutely true.
Speaker 3 (29:11):
So I think the next wave of T SELL engagers,
we have this what we call the Titan platform, which
is a CD eight guided T cell engager platform. The
lead program is directed against CD twenty, but we have
others that are coming in. We have a GPC three
Titan and others that are that are that are coming in,
(29:34):
and I think that platform is looking promising early days yet,
but but for an improvement in that therapeuticket index, you know,
so I think that's exciting. I've talked to you about
the envivo cell therapy. We've already shown some proof of
concepts that even in advanced solid tudors like happy to
cellular cancer. We presented data not this OSCO, but the
(29:55):
OSCO before with our GPC thee targeted car t for
HCC have a cellular cancer, you know, quite late line patients,
but quite impressive for.
Speaker 2 (30:10):
That and I was really excited, I have to.
Speaker 3 (30:12):
Say, yea and durability of response. So if we can
put that into an n vivo platform, then you can
start overcoming these challenges with the logistics that they was
talking about and the challenges with the cost of goods
for that. And again, so that's why we're excited about
that platform. And of course that's something that will have
to wait and see proven out over the next few years.
(30:34):
And then the other one I would call out is
again a cider kind again a CD eight directed IL
two program, which I think has the potential to be
differentiated from previous attempts to utilize what we know to
be a very important side kind that could be really
great combination partner with both the t SELL engages and
the cell therapy programs that we've got. So those are
(30:57):
just a few of my favorites.
Speaker 1 (30:58):
If you great, those are those last two areas are
the two areas that I'm going to spend quite a
bit of time on the clever cyto kinds and evolving
cell therapies, hopefully to try and get some my thoughts
on paper.
Speaker 2 (31:15):
Knowing that we're.
Speaker 1 (31:16):
Thirty seven minutes into this, let me move to ASCO
specific questions, and if we have time, I'll come back
to some of my other questions. Susan, the industry is
moving away from digit and you're going in the opposite direction.
So you know, I counted seven nine and fifty patients
in the ASCO in the Clickutrials dot Gov roughly. I'm
sure it's changed since when I looked and ten Phase
(31:38):
three trials.
Speaker 2 (31:39):
What do you know that the rest of the world
doesn't know?
Speaker 1 (31:41):
And I've seen the Gemini data, I've seen the TLO
four data. There's quite obviously something going on there, But
what do you know that the rest of the world
doesn't know.
Speaker 3 (31:51):
I'll come back to one of the sort of philosophical
approaches about oncology drug development in general, which I think
is important. First of all, is that failure with particular
targets or approaches something that Jose said failure is the
currency of oncology. Get over it, you know, but you
(32:12):
also have to learn from it. And so first attempts
about doing something don't always work, but you have to
look at you know, what can you learn from this.
What we've seen with this particular molecule wilbergosmik is that
the bispecific format, where you're actually binding those targets on
(32:32):
the same cell, appears to do something biologically different than
when you just introduce the two targets separately. And we've
seen that, you know, pre clinically, but also in what
I think are more relevant models. So the challenge with
the IO area has been that the models aren't you know,
great for predicting what you see clinically. And something that
(32:55):
Tom Schumacher actually introduced originally was sort of if you
take if you call patient derived organoids, segments of tissue
that you take from patients that you can grow for
a week or so in a culture medium that contains
still some of the immune cells taken from that patient's tumor,
(33:16):
and you look at the mechanism of action in those samples,
you get something that is more predictive of human biology
than you do in the classic space syndenetic models. So
what we have done is taken a whole range of
those built up some of that capability of a time.
We published in data at the City last year looking
(33:37):
at that and what it's showing. We're using interferm and
gamma production as a surrogate for a T cell proliferation
that's coming from those assays. But we've also looked at
does this predict for assets that both have worked in
the clinic and assets that haven't worked in the clinic,
and that model is reasonably predicted. What we've seen in
(33:58):
that is that real vergostama when it binds these two
targets on the same cell, produces better activity than when
you go just introduce a PD one and a tidget separately.
We've also seen that you know, the reduced FC function
that you've got with lvagostamig also seems to be differentiated
(34:23):
in that model compared to f C active modalities of data.
And then we just put that understanding of the mechanism
of action, understanding the level of t CUB proliferation, got
together with the emerging body of clinical data that we're
seeing in lung cancer, in billy tract cancer that you
refer to, in gastric cancer, habited cellular cancer, et cetera,
(34:46):
and we're building up a body of data that we
have that actually gives us confidence that first of all,
we're not seeing the enhanced side effects that sometimes seen
with other molecules that are in particular see active in
combination with chemotherapy regimens for example. Now you know, still
(35:06):
even the data that is out there with these with
these molecules, the adverse events aren't necessarily as high as
when you treat with a chemotherapy, but it's still causing
a discontinuation rate that may be affecting the long term
outcomes of patients on some of these trials. And so
we're encouraged by the fact we've got a very low
(35:27):
discontinuation rate for real vergostamik either as a monotherapy or
in combination with chemotherapy, or in combination with the ADCs,
So that's encouraging. Secondly, we are seeing you know, emerging
response rates, durability of response and landmark PFS rates, which
we find encouraging across the totality of the data. And
(35:49):
we think there's opportunity as well to further extend the
range of settings where you can get to an ADC
plus an IO that creates an opportunity to have a
differentiated red been compared with what's already out there. So
for all of those reasons, that's why we're investing behind
this molecule. I think there's there's opportunity.
Speaker 1 (36:07):
And yet, before I move on to a question for Dave,
I'm just going to take something you said that your
by specific is targeting molecules on the same cell. Is
that why you're not in PD one VEGEF and is
that why you're still excited by PD one or one four?
Speaker 3 (36:23):
So again, you know there's actually if you look at it,
there's quite a lot of data out there looking at
VEJEF added to io agents, right, And of course you
know when what we've done is look at those data
and see is this something that we can see that's
differentiated with the PD one vegeff by specifics compared with
what we'd see by adding a ved jeff targeted agent
(36:45):
to that background. And you know, and I would I
would just say that the jury remains out in that frame.
So if we look at the first line PDL one,
so first line nansmuscile lung cancer pedo one high group,
for example, we have data from the artmider One study
looking at real vogostamin and that setting where we've seen
(37:07):
you know, pfs and response rates in the same ballpark
as what's been described as well, So we think we've
got a competitive asset in that space. We've also got
an asset that we can combine with ved jeff as well,
and we've done that in the other cohorts of the
Gemini study. Obviously, exactly how that PFS benefit, which is impressive,
(37:28):
translates through to OS is still you know, a topic
for debate, And what we've seen typically across most of
the addition of veg jeff even onto an IO background,
is that you still get some deterioration of the effects
size between PFS and OS. We need to see exactly
what that that looks like. So you know, our approach is, look,
(37:49):
I think we can achieve much of this benefit by
adding a VEED Jeff directed agent into the regiments that
we're looking to do. And that's what that's what our
approach is.
Speaker 2 (37:59):
Okay.
Speaker 1 (37:59):
I think you've very consistent in saying that. So, Dave,
just thinking about the novelty of the Syriana six and
the innovativeness of the Syna six trial proof of concept
for ctDNA management guided therapy switch, do you expect continuing
to invest in using this kind of design going forward?
(38:20):
I mean, we saw the data at ASCO and you know,
so okay, some folks ask questions which we discussed earlier,
or does it depend on the ultimate outcome and the
uptake of this approach.
Speaker 4 (38:32):
Sim we certainly believe that blood based ctDNA guided decision
making will only increase as we move forward. I think
that in that regard, Serena six is a very exciting study,
not just because of what it represents for the patient
population that the study was designed for, but it creates
(38:53):
an opportunity for expanding the ambitions that we and the
field can have around how we can incorporate these types
of routine blood tests into the work that we need
to do to drive towards better outcomes. I think within
this context, we've got other studies that are looking to
(39:16):
incorporate ct DNA into the work that we're doing in
our own clinical trial settings. It's not it's it's it's
Susan could speak to this even better than I.
Speaker 5 (39:27):
It's not easy to do.
Speaker 4 (39:28):
We've we've tried this in in in lung cancer and
had to work through different assays and different ways of
of of of coming up with how we measure minimum
residual disease and other aspects with ct DNA. But I
do think more and more we will absolutely see this,
especially as we move into earlier settings where you know,
(39:50):
in metastatic or advanced disease SAM overall survival is the
gold standard and quite rightly what we in many instances
seek to pursue as we move into earlier stages of disease.
Speaker 5 (40:04):
To get to.
Speaker 4 (40:05):
Those overall survival endpoints requires a considerable amount of time
and large number of patients. In fact, being able to
have ct DNA MRD based approaches could very well represent
good surrogate opportunities as well for us to be advancing
medicines more quickly into patients that can benefit from them
(40:27):
straight away.
Speaker 1 (40:28):
I mean, I can think of a whole host of
things like I don't know, following cement emergence in an EGFR,
mutated patients while they're being treated, et cetera.
Speaker 2 (40:38):
Okay, and then Dave.
Speaker 1 (40:39):
Still with you, Destiny Bristol nine high cr rate long
stayble ow as tail. Dare I say, it suggests that
it's possible that some at a subset of her to
advance her to breast cancer patients can be dare I
say cured if that line stays flat, which is amazing.
(41:02):
Do you think you'd be able to identify these patients
and kind of what lessons did you learn from can
we take from the progress here to bring similar results
to other cancers.
Speaker 4 (41:12):
You talk about at the beginning of the podcast, some
of the changes that we've had a chance to witness
over the course of the last decade. I had the
great privilege and opportunity to work in the early days
on her septin, and I remember very very well when
we first had opportunities to show some of the adjuvant
(41:32):
data and the enthusiasm that we collectively felt for being
able to take a subtype of breast cancer that was
the worst prognosis and turn it into now a prognosis
that brought with it more hope for driving towards cure.
I have to say that the Destiny Bresto nine discussion
(41:55):
brought an equal sense of pride to me to be
able to hear from the podium belief that perhaps the
crs that we're looking with, if they remain durable over time,
start to introduce, as you just said, Sam, the possibility
of long term durable response and long term durable response
indeed could.
Speaker 6 (42:14):
Be cures today.
Speaker 4 (42:15):
I don't know that we have the opportunity to be
able to know which patients are likely to experience that response,
which is the reason, among others, why it's really important
for the best therapy to be used first. I think
that in breast cancer, one of the things I've observed
is that because there are a multitude of options that
(42:39):
are available to patients and the physicians who are treating them,
there can be I think, very thoughtful, but at times
perhaps a little academic discussions around sequencing and optimal approaches
towards thinking about therapies over time, and indeed that's very important,
But we do know time and time again that bringing
(43:01):
the best therapy first and upfront is oftentimes what results
in the best outcome for patients. And in this particular instance,
I think that we heard the community pretty unanimously clear
that the Destiny Breaston nine data with over forty months
of median pfs being presented, you compare to where we
(43:23):
were ten years ago, we were at four months, and
so just the progress that's been made over that and
with the complete response rates that we saw pretty breathtaking.
And remember one last important piece, over a third of
patients being treated for breast cancer in the frontline setting
of metastatic disease, unfortunately don't get an opportunity to see
(43:46):
a second line therapy, either because they progress, or they
pass away, or their performance status gets to a place
where they're not able to take therapy. So not only
are you moving the best therapy up front, but there
are more patients who can potentially benefit from that therapy
because you're in an earlier setting of the cancer.
Speaker 3 (44:06):
So, Susan, did you want to say something, well, just
that of course, one of the things we want to
then do is take that setting and learn about which
patients you know, potentially benefit. I do think this is
another setting where technologies like ctDNA can help inform the
patient individualized pathway through that. So we're going to have
(44:30):
to generate some of those data and understand that. And
I also think these trajectories of change that you can
put for an individual patient is also something that's suitable
for some of the AI modeling to approach and help
doing that. So I'm optimistic that we can take this
as a starting pact completely with Dave that right now,
this is the data that we have, and if it
were me, I'd want to have that best treatment at first.
(44:54):
But I think also we can study this and study
this setting and try and help inform over time, you know,
how you make some of those choices.
Speaker 1 (45:03):
And so actually, in an interesting related point, Susan or Dave,
one issue, if you want to call it that in
the study was the high proportion of denovo metastatic patients.
And I can't remember if it was you who brought
it up or the discussing or presenter. I can't find you.
I can't recall. Now this reflects a shifting obviously reality
(45:24):
in more patients. Again, that word cure and extended emissions.
Is this dynamic something that's likely to grow more common
with more effective agibate new agumant treatment. Going back to
something you said earlier, also, how do you track and
think about this and how do you think it will
impact how drugs are developed in the space because timelines
(45:45):
have become also quite large.
Speaker 3 (45:46):
Yeah, which is why some of these you know, intermediate
clinical endpoints can be really quite useful in doing that.
But you know, if we are successful in diagnosing more
cancers earlier, and we are successful in developing better NEWT
and perioperative regiments, then the expectation is that the percent
of those patients that then go on to despite adjuvant therapy,
(46:10):
despite surgery, et cetera, then progress is going to decrease.
And so you know, you would expect that over time
the proportion of patients in the first line metastatic that
our denovo will increase. So you know, again I think
in the current context, what I would say is, because
of the aging population around the world, the incidence of
(46:33):
cancer is still increasing. So whilst you know, even if
we're improving the cancer mortality rates, the total burden of
cancer is not decreasing yet. So you know for the
next you know, two to three decades, that demographic is
you know, that's built in, and so there will be
(46:55):
remaining plenty of opportunity if you like to treat patients
in both the early stage setup and in the metastic
setting for many of the cancers that were treating. But yes,
you know, as an overall trend, you'd expect the proportion
that our denovo to increase over time.
Speaker 4 (47:09):
Just on a very specific destiny breastone nine point. I
had an opportunity to hear many investigators comment that the
percentage of patients that were denovo and that study was
seen by them as a strength because in fact reflected
real world the patients that are presenting within their clinics
and within their hospitals, and that that is indeed a
(47:31):
patient population that they were keen to understand how the
treatment within her TOO and Producer map would be best
incorporated into that population.
Speaker 1 (47:41):
Right, we've got a few minutes left. Thank you Dave
for that, and thank you so far for all your insights.
I'm going to do some rapid fire questions. This one's
a thorny one, I think, I asked Susan at the
AACR pre event in April whether you'd sensed any tangible
change in your interactions with the FDA, and I think
you gave a very clear answer, no, has anything changed
(48:04):
since not yet?
Speaker 2 (48:07):
Okay, good, you see rapid fire.
Speaker 1 (48:09):
And have you felt any changes yet from the cuts
in an IH and the overall funding of science in
general in the US.
Speaker 3 (48:16):
Well, I just and this is not going to be
quite so quick. My view is that at the moment,
there's you know, an acceleration, as I said, in the
pace of innovation and in science. I just philosophically do
not feel that this is the moment which to back
off from investment in science, but actually to accelerate and
come behind it. That's what drives innovation in all of
(48:40):
the countries you know, around the world. Investment in the
science base, investment in the innovation or reward for innovation
you know, you know, delivers improvements and benefits for patients
and for those countries in terms of the world generations. So,
you know, philosophically, I think that's that's the approach that
that you know, we would support.
Speaker 2 (49:03):
But you haven't.
Speaker 1 (49:04):
I mean, I don't know where how long it takes
for these things to impact AstraZeneca because it's you know,
a lot of this is basic.
Speaker 3 (49:10):
Well, there's there's there's often you know, multiple years for
scientific you know, basic science discoveries to you know, flow
through into subsequent you know, often it comes through into
technological improvements that enable new discoveries, et cetera, et cetera.
So there's a there's a bit of a like time
on that. But again, you know, I would encourage all
(49:34):
countries that the investment in the science base and the
academic base is an important part, but also that needs
to be then you know, link linked to the innovation
and the investment in the life sciences sector, the enablement
of access to venture capital, et cetera, in order to
help companies start and strive and prosper. So all of
(49:57):
those things that I think important part of the ecosystem.
Speaker 1 (50:01):
Success, especially given I've got two kids who are trying
to be scientists. So I look forward to a positive
future for the Pascales often spoken about how impressed he's
been with science in China and drug development landscape. What
exactly changed over the past five to ten years.
Speaker 6 (50:18):
I can take a quick start.
Speaker 4 (50:20):
I think that one of the there's been several things
that have happened. One of the things that has happened
is that there's been really a modernization of Chinese FD eight,
and I think that the approval path has become much
more clear for medicines to be able to come to
market in China. Secondly, there's also been an important improvement
(50:43):
in the public payer modernization that's taking place. Still a
lot of progress that needs to be made there, but
more and more access being made. I'll let Susan speak
to some of the scientific elements, but the reason I
highlight those two dimensions is I think that, linking back
to your previous question, the US has led the life
(51:04):
sciences industry for decades, and I think that as a
result of that leadership position, there's been better access for
patients in the United States to innovative new medicines. There
has been greater number of clinical trials, and that the
time to public reimbursement for new and innovative medicines is
(51:29):
the shortest that it is across the globe. And I
think that in cancer in particular, we can see that
the outcomes have followed that, and so I think that
it's really really essential for countries that want to be
leaders in the life sciences space to ensure that they
are spending a fair share of their GDP on innovative medicines,
and that they are recognizing that that investment translates into
(51:53):
access and outcomes for patients. Let Susan speak maybe about
some of the other things she's seeing on the science
side within China, but I think those other dimensions are key.
Speaker 3 (52:02):
So I mean, China used to build on what David said,
has absolutely invested in the quality of the science at
the top universities over many years. And you see now
you said before, I think in terms of the citations
that there are many, you know, really very high quality
scientific publications that are coming in. They've also invested in
(52:25):
providing support, if you like, for their own life science companies.
They get support for sort of capital investment over a
period of time and support to access to funding. And
then also they've got reflux back into China of many
well trained scientists but with experience of working in the
(52:50):
West that has happened. And then with all of these
things together, they've very rapidly put that together into the
ability to actually create companies that can move at speed.
The other thing that's changed is the regulatory environment in China.
You know, five to ten years ago, it used to
take much longer in China to get a clinical trial open.
(53:11):
Now you can do it at the same speed in
China as you can in the US, or perhaps even
faster than you can in Europe. You know, So that
these things that are happening, and particularly the example in
the cell therapy area, which is one area where China
is actually leading in the innovation. They have this system
(53:31):
for allowing investigative initiated studies at single institutions that can
open very rapidly, and that allows you to iterate and
learn from the clinical stage of development very rapidly. And
that's why technologically and scientifically, you know, many Chinese companies
are at the leading edge in terms of the cell
(53:52):
therapy innovation. So I think it's just an example of
they've taken approach where saying this is something where we
want to be, you know, moving up the country ranking,
and they've taken a systematic approach to removing the barriers
to that and enabling the investment. You know, I think
(54:14):
that's a very similar approach that could be taken in Europe,
it could be taken in the in the US, and
just look at those areas where some of the barriers
can be removed and enable and unleash the innovation that
exists in all of these regions. There's no reason why
we can't do it, but you have to have the
will to do it and the will to think about,
(54:35):
you know, what those barriers are and how we can
improve on them. So my aspiration is that all areas
will look at, you know, how they can improve on
some of these and enable fast. You know, at the
end of the day, you know, it's cancer patients that
can benefit from some of the innovation that we've got
for and they haven't got the time to wait. So
(54:55):
I'm very enthusiastic about things that can help bring down
the barriers to drive in the innovation.
Speaker 1 (55:00):
I couldn't have wished for a better ending to a conversation,
to be honest with you, what maybe one last question
before I say goodbye, will there will there be an
eighth year of plenaries at ASCO.
Speaker 3 (55:11):
Well, Listen, I don't measure the success of the R
and D organization just solely on that metric. We're very
proud of what has been achieved already, but I think
the danger is for either complacency or said, look, you
know and that the ASCA plannary is always a highlight
because really shows things that are pushing the boundaries. If
(55:34):
we can possibly strive to do that again in the future,
I'd be absolutely delighted. But let's wait and see how
the Chians plan out.
Speaker 2 (55:42):
I look forward to.
Speaker 4 (55:43):
It, and you know, and Sam, right now, we really
stay focused in with those plannaries, just just just only
a few days behind us on making sure that those
plannarias result in approvals in reimbursement and that we're able
to get medicines to the patients who can benefit from them.
Speaker 6 (56:01):
That's what we stay focused on right now. In twenty
twenty five.
Speaker 1 (56:04):
Well, my fingers are cross for you and I'm really
excited to continue to watch very closely what do you
guys do. Thank you very much for taking time to
talk to me, Susan Dave. This has been an absolute pleasure,
and thank you. Let's see if you liked it, we
can try and do it again next year.
Speaker 3 (56:20):
Thank you very much.
Speaker 5 (56:20):
Thank you. Sam
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.
I'm a senior pharmer analyst at Bloomberg Intelligence, the in
house research arm of Bloomberg. I am thrilled to be
talking to Susan Goldbraid and David Frederickson from AstraZeneca today
(00:37):
with our focus on oncology hot on the heels of
the ASCO Convention, which is always a bit of a
whirlwind when it happens and you come out the other end.
Speaker 2 (00:49):
Trying to organize your thoughts.
Speaker 1 (00:51):
So this is an ideal time for us to be
doing this, and I'm really really delighted to have both of.
Speaker 2 (00:58):
You on the call now.
Speaker 1 (01:01):
Just to introduce, I doubt there's anybody out there who
doesn't know who you are. So Susan Goldbraid is Executive
Vice President of Oncology Hematology R and D at Astrosenica,
and Dave Fredrickson is Executive vice President of Oncology Hematology
Business at Astroseneka.
Speaker 2 (01:18):
So we have the.
Speaker 1 (01:19):
Two leaders here which quite clearly have amazing teams because
of the continuous progress that the company is making. I'm
going to start off, if I may, by just talking
some big picture strategy here, susan Astro. Seneca's legacy has
been in small molecules, right, I mean, you're the leader
(01:40):
in lung cancer. Is you off our positive lung cancer
with Tagriso. But now the company's focused more on novel modalities.
Speaker 2 (01:47):
What's changed? What has shifted here? Or are you still
looking into small molecules?
Speaker 1 (01:53):
Is this dare I say it an effect from the
IRA small molecule penalty pill penalty? Do you want to
just talk us through that a little bit?
Speaker 3 (02:02):
Yeah? So, as you say, we have got a good
chat record of delivering medicines that are from the small
molecule background. But you know, increasingly the range of options
that are available through more sophisticated putt in engineering, development
of modalities like te sell engages and the development of
(02:23):
modealities like antibody drug conjugates means as a range of
opportunity for medicines in those spaces as well. So it's
more that the opportunity set has grown in things that
are larger than small molecules. But of course, with the
Swena six data that were presented at ASCO. You know,
it's not that we're backing away from small molecules in
any way, shape or form, and we have other drugs
(02:45):
like zoriprib, which is part one selective molecule in phase
three is another example. But there are lots of exciting
new models that are coming through, as I've mentioned, and
I think in terms of the thinking about the impact
of the IRA and tail end of the life cycle curve,
if you like, the thing that I worry about more
(03:06):
than loss of exclusivity or that is this term that
I introduced at the ACM meeting of loss of relevancy,
that the pace of innovation is increasing so much now
that actually there's an opportunity for disruption of things that
have already been established during their life cycle rather than
at the end of their life cycle. So that's what
(03:27):
I think we have to keep an eye on, and
that's why we're investing, you know, not just in the
programs that we need to deliver for approvals in the
next four or five years, but also in those modalities
that will deliver beyond that time period. And that's why,
for example, continued investment into the cell therapy area including
the recent acquisition of Isobiotech to access in vivo cell
(03:52):
therapy modality for example. That's very important as well, because
you know, I can see that that has potential to
be a disruptive force. So that's the philosophy really, rather
than one about the current view on time period until
you start having negotiation from the IRA.
Speaker 2 (04:11):
Well, I love that.
Speaker 1 (04:12):
I love that phrase when I heard it first time
you were on that panel, when you mentioned it at
the PREACR meeting. The problem for us analyst is that
loss of exclusivity is relatively easy. You see a date,
you assume it's going to go. You maybe add six
months for some kind of extra exclusivity. Then you do
a generic erosion lots of relevance. That's a much harder
(04:33):
tea to calculate and workout. But so thank you very
much for doing that and making our lives even harder
now talking about lots of relevance, of course, it.
Speaker 2 (04:41):
Cuts both ways.
Speaker 1 (04:42):
Some other company might change the relevance of your compound,
and you might do the same to others. So you've
got a whole bunch of readouts coming out this year
over the next.
Speaker 2 (04:50):
Twelve months, So we're going to go exactly.
Speaker 1 (04:51):
Twelve months to next asco what are the ones, what
are the hot ones that if you could do that,
I'm not asking you to pick your drugs, I'm asking
you to pick your particular readouts here.
Speaker 2 (05:02):
That you're that you're looking forward to. Anything is going
to make a difference to our next question.
Speaker 3 (05:07):
Yeah, sure, we'll just extend the timeline a little bit
to the end of next year so that we're not
giving more specific guidance than is normal for us at
this point in a year. But of course there's a
lot of interest in the evans A study in first
line nonsmal cell on cancer. This is the combination of
datchaway our chrope two based ADC with infimsy r PDO
(05:30):
or antibody in the first line setting a non SMaL
cell lung cancer. So my view is that I guess
perhaps disproportionate focus, but beyond that, actually, it was so
pleased to see the Niagara study be there last year
that we presented the planary at ESMO, and we now
have the Vulgar study which looks at the combination of
(05:51):
infimsy and importuma prodota in that perioperative setting in bladder cancer.
So that's an exciting study. We have another more in
her to read out. We've already announced positive top line
results for Destiny breast eleven in the new agudant setting,
but we looking forward to the results of Destiny BREASTO five,
(06:13):
which is in the post near agulant setting in early
stage her two positive breast cancer. Of course, extending from
the Serena six data that we had ADASCO, this is
the potential for the Serena four data in the broader
first line population of your positive advanced breast cancer. And
then the next day you c that people aren't yet
(06:35):
paying as much attention to, which is you know a
Zedden nine oh one which now has a name son
citemeg for doton, which we call sonny V. That's in
the Cloita GASTRICO one study in second line plus gastric cancer.
Speaker 2 (06:52):
What's the mechanism there.
Speaker 3 (06:54):
That's a it's targeting chlaudine eighteen point two and it's
got an MMAE based payload on that dragon. Again, we
had encouraging response rate, endurability of response that was seen
and we've taken that into the light line. But there
will be you know, other investments that you'll see coming
with building on that molecule, we have the Emerald three
(07:14):
study for infemsy and habita cellular cancer, and then in addition,
in the EADI far mutant subset of lung cancer, we've
got the Chropian line fifteen study, which is a combination
of data away and ossimertanib in that second line, post
Surgen Tki in the first line.
Speaker 1 (07:34):
Yeah, we've been I've been listening and thinking and talking
to as many physicians as I can about this increasingly
complex world of EGOFAR mutiated lung cancer. Because you had
physicians had one choice until quite recently, and now suddenly
flora to Myriposa mariposa too, and then you get all
the second line options, maybe even PD one VEG who
(07:57):
knows right, So, but I'm going to turn to Dave.
Now you've listed a series of readouts. You've also got
an incremental approximately thirty billion, let's say thirty five billion
or so, whatever the exact number is to get to
your eighty billion dollar target. Can you just Dave took
us through how much of that you think could come
(08:17):
from oncology, and then how many of these readouts are
particularly important for that target?
Speaker 3 (08:25):
Thanks?
Speaker 4 (08:25):
Sam Well when we reported out earnings at the end
of last year, and indeed, when we take a look
at first quarter, about forty percent of total company or
enterprise revenues come from oncology. So certainly, as Susan and
I look out towards twenty thirty and beyond, we expect
oncology to be at least at that level of composition
(08:49):
of sales. So I think that, you know, we should
look forward to and expect, just in rough measures, that
perhaps maybe half of the growth that we want to
get to from where we are today to this eighty
billion ambition that we set out for twenty thirty would
come from oncology. And I think that there's two really
key drivers of that, and we saw both of those
(09:10):
at play at this most recent ASCO. One is that
we've been working very diligently to maximize the clinical development
plans for our existing launched assets. Two examples of those
obviously we saw INFINSI with the Matterhorn data at ASCO,
where we have an opportunity to bring in FINSI into
(09:32):
a perioperative curative intent gastric esophageal junction cancer setting. INFINSI
is one of our fastest growing inline medicines that we
have within oncology. That is coming on the heels of
a number of first in class, best in class studies
that we've been investing behind. And then you also saw
(09:53):
on Her too, as Susan mentioned too before with the
Destiny Bresto nine data, again a multi blockbuster indication spansion
opportunity on two medicines that we already have in hand.
So that's the big first piece, which is maximizing those
clinical development plans. The second is obviously launching new medicines.
AstraZeneca's laid out a objective to contribute twenty new medicines
(10:16):
by twenty thirty in order to get to that eighty
billion dollar ambition, and then to have a sustainable pipeline
in order to drive business thereafter. And hopefully we will
be able to see the approval of camas Estrant on
the back of data from Serena six. Also, certainly breakthrough
therapy designation being a good indicator that the FDA sees
(10:39):
these as important data as well. And we've got multiple
five billion dollar plus potential new assets that we see
in the pipeline. Camas Estron is one. Also, are IOBI specifics,
which I'm sure we'll talk a little bit more about later,
but Revalgustamig, which is PD one legit by specific Volustomig,
(11:02):
which is a PD one CTLA four serup rib small molecule.
Back to your previous question, in the park space, really
building off of Limparza and our pioneering work there, and
then in the hematology space, serav Atamig, which is a
CD nineteen CD three T cell engager that we're taking
(11:22):
into multiple hematologic settings, and AZD zero one two zero,
which is our car T therapy, which we'll launch into
multiple miloma first, but where we've got ambitions to expand
beyond that. So we've got seven assets that are yet
to launch that we think have multi blockbuster potential to
(11:44):
drive us not just to twenty thirty, but really importantly
sustainably in the next decade.
Speaker 1 (11:50):
Thanks for that, Dave. One of the issues, of course,
you're facing is that some of these are going into
really crowded spaces. Do you feel that they're SACD nineteen
City three or the Mylomo asset. Do you feel that
you think you're going to have sufficient differentiation to be
able to get take indrois or are they just a foothold,
(12:11):
And then there's of course the I and I applications
of a whole bunch of these inflammation and imienology.
Speaker 4 (12:17):
I mean, at the most important strategic level, we go
through about every two weeks investments into our Phase three
studies through what we call portfolio Review Committee. And one
of the key areas of focus when we make capital
allocations and we think about clinical trials is do we
have the opportunity to be first in class or best
(12:38):
in class? Back to Susan's point about loss of relevance,
there's nothing worse than launching irrelevant. That's instant loss of relevance.
And so we've been working very diligently to ensure that
we've got some best in class competitive intelligence capabilities. We
work to make sure that we are bringing the most
(13:00):
innovative studies that go into what we call white space,
space that's not occupied by other competitors. And we also
work to execute as best we can to be first
in places that are deeply competitive. I would say beyond
those dimensions, certainly, we think that we've got opportunities to
(13:20):
create advantage through a couple of core areas that we
work on. One of them is we think that we've
got differentiated patient identification approaches, so certainly how we approach
computational pathology things like Serena six, which was using an
opportunity to identify patients and incorporating that precision medicine approach
(13:41):
into our studies as one. And combination approaches is another
area for advantage where we see opportunities to combine multiple
assets within the Astrazenica portfolio to be able to do
things more quickly and indeed perhaps combinations before competitions able
to engage in the same sets of studies and just.
Speaker 3 (14:01):
Entering us specifically about the serivatimik, the CD nineteen, CD
three and Azada one two oh or CD nineteen b
CMA carties. So let me just give you some examples
that illustrate the points that Dave was saying. So Savatamig
was designed with lower affinity CD three to have a
better therapeutic index in terms of cytocin release syndrome, but
(14:24):
because it also target CD nineteen, which has a broader
range of expression across B cells, has a potential for
differentiation from some of the CD twenty based decil engages
that are currently there and Actually, we've presented some data
at ASCO in the fuse large B soulen theoma, which
as you go up through the target dose range, you know,
(14:46):
shows improvements in a complete response rates that really I
think are very competitive with what you've seen with other
molecules out there, and we'll be presenting some data EHA
later this week in a the bustic leukemia with also
I think very competitive al rates. So the design of
the molecule was selected to try and provide that differentiation.
(15:09):
And then again the dual car targeting that we've got
with as a one two plus the fastcar manufacturing process
gives it a really nice profile overall. You know, we
presented some data at ASH last year, small numbers admittedly,
but in newly diagnosed multiple myeloma with patients that are
(15:31):
high risk. You know, we saw one hundred percent CR
rate and ninety five two hundred percent MRD negativity rate.
So I think it can be very competitive, even though
as you rightly point out, that field is a very
competitive one.
Speaker 1 (15:46):
Let me let me just move on to a couple
more questions. I'm now realizing that we needed two hours
for this, but never mind. So you've had a bunch
of recent term readouts that you're not only improving or
potentially improving standard of care by drug replacements, substitutions, et cetera,
as is the usual case, but really focused on even
(16:06):
changing the practice. So SERENA six testing for ESR one
emersions right, advans are using QCs, You're really at the
edge of that marriage of diagnostics and.
Speaker 2 (16:20):
Therapy.
Speaker 1 (16:21):
And so I wanted to just get a feel for
what's your thinking behind this approach and did the drugs
just lead you here or is there a broader process
going This is how we're going to differentiate and help
patients better.
Speaker 3 (16:34):
Yeah, well, I think there's a background philosophy which you've
seen not just in these two programs, but really you
know with the approvals with them PASA and with SRISA,
which is that you know, understanding the right patients to
treat within each patient population is a fundamental part of
that differentiation process. So we always work on that and
(16:56):
at an early stage, and we have also not had
not just had success in doing that within the R
and D space, but partnership with Dave's team, you know,
working for some years before the potential launch to make
sure that we have the ability to then deliver it
into the commercial space and drive that uptake. You know,
you forget now, but looking back, having a next gen
(17:20):
sequencing based ctDNA test for example, wasn't obvious at the
time that we started doing that within the clinic called trials,
and so I think that's analogous to the use of
quantity to continue scoring, which is based on AI machine
learning ability with computational pathology. We acquired a company, Definians
(17:42):
several years ago, which was originally trying to look at
biomarkers for IO mechanisms of prediction. When we then did
the deal with Diretyusankia for access to and her too
and then subsequently for data d x T now de way,
you know, it was obvious to me that we were
(18:04):
going to need biomarkers for these what are you know,
self surface directed targeted therapies in order to optimize the
benefit risk, and so we worked with that computational pathology
team to see if there are ways that we could
better identify those and understand it. So that was a
you know that QCs biomark has been five years in
the in the development, so it absolutely is not just
(18:27):
because we saw what we saw entropy and Longo one.
It was a philosophy from the time of the partnership
initiating that this is something that we're going to need
an investment behind it at risk to do that. And
I think with the Serena six data as well, this
is a is going into a white space, as Dave said,
which is it was a way for us to accelerate
(18:50):
into that first line setting and get experience in a
place where we thought you're most likely to be able
to show the improved benefit risk. In this case, we
do think that chemists astro will also work in the
broader wild type patient population, but this gave us an
opportunity to get early into the first line and so
(19:11):
it was very much, you know, an opportunistic approach for
chemis astron.
Speaker 1 (19:18):
I mean, that's eminently sensible, but unfortunately our world doesn't
just follow sensible stuff, right, so we have a you know,
I want to move to Dave here quickly. You think
about QCs, the NMR and es R one testing for
Serena six. These eminently sensible, but how confident are you
(19:39):
that payers and physicians and we heard the questions when
you presented the Serenus six data with regards to the
number of tests or that have to how often do
we test patients to know that they are the s
R one is emerging, et cetera.
Speaker 2 (19:53):
How confident are you that you'd.
Speaker 1 (19:55):
Be able to get them on the same path on
this journey, not just in the US, but let's face it,
Europe and China are maybe I don't know, easier and
more difficult.
Speaker 4 (20:07):
Well, I have a great deal of confidence Sam that
when clinical data are compelling, that we have worked together
in the markets with stakeholders that we are operating in
to be able to create access to these important biomarkers.
And really most of the portfolio that we've launched for
(20:30):
the last ten years has some type of biomarker associated
with it. So in that regard, there's certainly a deep
amount of experience that we have I think a couple
other important pieces.
Speaker 5 (20:41):
You know, a lot of times.
Speaker 4 (20:44):
Biomarkers are relevant for research purposes, but when they become
relevant for making treatment and clinical decisions, that's when we
start to see that the sense of urgency really increases. Also,
the cost will only go down from here. We know
that that's true across other areas that we've looked at
(21:04):
and why is that, Well, it's because different parts of
the globe and different companies look for ways to create
resource appropriate solutions to deliver decentralized approaches to diagnostics. There's
partners that we work with like Sophia Genetics who's working
to expand access to tissue and liquid panels through their
(21:30):
work in collaboration with memorial slum kettering even examples and
this is a bit of a tangent, if you will,
but it's relevant when you take a look at the
work that cure Ai does in order to be able
to take lung cancer scans or X rays and turn
them into the equivalent of CT scans in terms of
the value that comes out of from for lung cancer screening.
(21:52):
We see so many different opportunities where technology is creating
resource appropriate, decentralized approaches to being able to deliver these
kinds of precision medicine approach.
Speaker 5 (22:03):
So there will be a learning curve.
Speaker 4 (22:05):
We are going to absolutely need to work together in
all of the markets that we launch in in order
to ensure that there is supply of ESR one mutation
testing and QCs in order to meet the demand that
we think that these studies either have with Serena six
or could with a von Zar demonstrate right. But I
(22:29):
also have confidence that it's a path that we understand
how to move ourselves down.
Speaker 2 (22:34):
This actually etc.
Speaker 1 (22:35):
Is very well into their next question for you, Dave,
In terms of oncology treatment in ten years time, I
think one way to think about is look back ten years.
Speaker 2 (22:42):
It's not exactly ten years.
Speaker 1 (22:44):
That Tagrisa has been in the market, but EGFR patient
came in with Lunkhan said they had one choice, physician
made a decision, patient went home. Now you have to
perhaps think about them from a brain mets sitting, ecoc sitting, etc. Right,
how many what's the burden of disease when it comes
to choosing? How do you see this in tenuous time?
More disease segmentation, more cures one hopes, more diagnostics by markers.
Speaker 2 (23:09):
Where are we? What else is there to think about it?
Speaker 1 (23:11):
And that makes your life and your cost higher. Although
you just said that these things get cheaper as time goes.
Speaker 4 (23:17):
On, Well, yes, I see more of those things, and
after I offer a response, it certainly welcome Susan in
on this.
Speaker 5 (23:25):
You know it's interesting.
Speaker 4 (23:25):
Eleven years ago Susan and I had an opportunity to
launch Limparsa together, and the first global launch for that
was in the United States, actually in Denver, Colorado, where
we came together. And we've had an opportunity to watch
many trends that were really just kind of sparkles in
(23:45):
our eye and imagination of the future really begin to
take hold and really progress along. And I think we'll
see more and more of that as we look to
the future. So we are absolutely moving beyond a one
size fits all a part So yes, more precision medicine.
We are working hard to move into earlier settings of
(24:07):
disease where we can drive to cures. What are some
of the specific things that we're doing. Novel ADCs are
replacing backbone chemotherapies. I think when you take a look
at discussions that were happening in twenty twenty five at ASCO,
it's not about will ADC's deliver on their promise, but
how do we incorporate them into treatment? How do we
(24:27):
think about sequences, sequencing, how can we think about best
ways of personalizing for the patients who can benefit. Secondly,
we talked about this before, but next generation immunotherapy agents
will absolutely represent to raise the bar to deliver better
responses to io than what we've seen with checkpoint inhibitors.
(24:47):
To date, checkpoint inheritors have made an enormous amount of progress,
but too few patients respond and they don't respond long
enough in all of the instances. There's a great opportunity
to do even more to enhance and rebuild the immune system.
Speaker 5 (25:00):
There'll be advances to that point.
Speaker 6 (25:01):
In cell therapy and T cell engagers.
Speaker 4 (25:04):
Certainly, cell therapy has represented an enormous step forward in
terms of breathtaking responses in terms of some of the
complete responses that we see in studies, yet it's been
limited largely to hematologic malignancies. The opportunity to bring that
into solid tumors and actually outside of oncology into the
autoimmune space is incredibly exciting. And then also can we
(25:27):
use T cell engagers to rebuild the immune system in
a way that perhaps is not nearly as supply chain
constrained as what we get through some of the autocar approaches.
The power of combinations is a fourth major trend, and
we talked about this before, but we think combinations will
transform survival and cancer, and in particular, the last piece
(25:49):
fifth is early intervention. By moving earlier, we see the
greatest opportunity to be able to drive towards what hopefully
are long term, durable responses, which.
Speaker 6 (25:59):
We have the opportunity energy to describe as cures.
Speaker 4 (26:01):
So yes, in the future, more cures, more segments, more personalized,
more combinations. And the way that we're able to make
sure that that doesn't just result in so much complexity
is I think that we've got to really embrace technology
that's going to allow for us to be able to
(26:22):
have physicians be aided in their clinical decision making process.
There's work that we need to do on moving from
individual diagnostic testing to multiplexing. There's a number of things
that we do to try to capitalize on scale that
we have in tumor types like breast cancer, lung cancer,
GI cancers, to be able to find ways to ensure
(26:45):
that we're able to maximize each of these individual indications
and assets and opportunities for patients and do it in
a way that is taking advantage of a cost base
and an intellectual capability base that's already built up within
these areas.
Speaker 2 (27:00):
You know, Dave, that sounds like AI to me. If
you could put AI sticks.
Speaker 1 (27:04):
Now that's a phrase that's overused and in some cases underused.
I don't know what we'll we'll see how that all
pans out, Susan, did you want to make a comment
on this.
Speaker 3 (27:13):
Well, now, obviously, I think one thing to think about
with these combinations that we're thinking is not that everything
gets dosed on top of everything, but you can actually
create kind of regimens. I still think that you're going
to need kind of debulking regimens, if you like, for
which I think combinations of either the ADCs or already
conjugates together with some of the new immunotherapy agents you know,
(27:36):
can help to do that. And you see evidence for
that in some of the emerging neo adjutant data we presented,
for example at the Near Coast to study at ASCO,
which is an ADC datid HD plus io and with
that with which was infimasy. With that combination, we kind
of doubled the paths and doubled the major pathologic response
(27:58):
rate compared with what you got with ioplus chemo and
the A G and trial, if you like. So there's
an illustration of the fact that you can do that.
But still, you know, even if you've got into that setting,
some of the patients will relapse from that, so you
probably still need some consolidation. And this is the place
(28:19):
where I think if you can get people into a
patsy R or MRD negative state even after to say
first line metastatic disease, that's the place where I really
think that the cell therapy is most likely to then
show the long term benefit. So you know that it's
not just about everything on top of one another. It's
(28:41):
the you know, induction and consolidation maybe the way to
think about it.
Speaker 1 (28:45):
I think you've answered two or three questions all in
one go there. If you wanted to just pick one
or two moas that you have in your pipeline be
in phase one, that's that you would put in the
category of a twinkle in your eye that in teniest
time we've got to look back and.
Speaker 2 (29:00):
Say, wow, what are you hopeful for?
Speaker 1 (29:02):
Of course, you know we all know how biology and
especially in oncology makes us humble, but that's absolutely true.
Speaker 3 (29:11):
So I think the next wave of T SELL engagers,
we have this what we call the Titan platform, which
is a CD eight guided T cell engager platform. The
lead program is directed against CD twenty, but we have
others that are coming in. We have a GPC three
Titan and others that are that are that are coming in,
(29:34):
and I think that platform is looking promising early days yet,
but but for an improvement in that therapeuticket index, you know,
so I think that's exciting. I've talked to you about
the envivo cell therapy. We've already shown some proof of
concepts that even in advanced solid tudors like happy to
cellular cancer. We presented data not this OSCO, but the
(29:55):
OSCO before with our GPC thee targeted car t for
HCC have a cellular cancer, you know, quite late line patients,
but quite impressive for.
Speaker 2 (30:10):
That and I was really excited, I have to.
Speaker 3 (30:12):
Say, yea and durability of response. So if we can
put that into an n vivo platform, then you can
start overcoming these challenges with the logistics that they was
talking about and the challenges with the cost of goods
for that. And again, so that's why we're excited about
that platform. And of course that's something that will have
to wait and see proven out over the next few years.
(30:34):
And then the other one I would call out is
again a cider kind again a CD eight directed IL
two program, which I think has the potential to be
differentiated from previous attempts to utilize what we know to
be a very important side kind that could be really
great combination partner with both the t SELL engages and
the cell therapy programs that we've got. So those are
(30:57):
just a few of my favorites.
Speaker 1 (30:58):
If you great, those are those last two areas are
the two areas that I'm going to spend quite a
bit of time on the clever cyto kinds and evolving
cell therapies, hopefully to try and get some my thoughts
on paper.
Speaker 2 (31:15):
Knowing that we're.
Speaker 1 (31:16):
Thirty seven minutes into this, let me move to ASCO
specific questions, and if we have time, I'll come back
to some of my other questions. Susan, the industry is
moving away from digit and you're going in the opposite direction.
So you know, I counted seven nine and fifty patients
in the ASCO in the Clickutrials dot Gov roughly. I'm
sure it's changed since when I looked and ten Phase
(31:38):
three trials.
Speaker 2 (31:39):
What do you know that the rest of the world
doesn't know?
Speaker 1 (31:41):
And I've seen the Gemini data, I've seen the TLO
four data. There's quite obviously something going on there, But
what do you know that the rest of the world
doesn't know.
Speaker 3 (31:51):
I'll come back to one of the sort of philosophical
approaches about oncology drug development in general, which I think
is important. First of all, is that failure with particular
targets or approaches something that Jose said failure is the
currency of oncology. Get over it, you know, but you
(32:12):
also have to learn from it. And so first attempts
about doing something don't always work, but you have to
look at you know, what can you learn from this.
What we've seen with this particular molecule wilbergosmik is that
the bispecific format, where you're actually binding those targets on
(32:32):
the same cell, appears to do something biologically different than
when you just introduce the two targets separately. And we've
seen that, you know, pre clinically, but also in what
I think are more relevant models. So the challenge with
the IO area has been that the models aren't you know,
great for predicting what you see clinically. And something that
(32:55):
Tom Schumacher actually introduced originally was sort of if you
take if you call patient derived organoids, segments of tissue
that you take from patients that you can grow for
a week or so in a culture medium that contains
still some of the immune cells taken from that patient's tumor,
(33:16):
and you look at the mechanism of action in those samples,
you get something that is more predictive of human biology
than you do in the classic space syndenetic models. So
what we have done is taken a whole range of
those built up some of that capability of a time.
We published in data at the City last year looking
(33:37):
at that and what it's showing. We're using interferm and
gamma production as a surrogate for a T cell proliferation
that's coming from those assays. But we've also looked at
does this predict for assets that both have worked in
the clinic and assets that haven't worked in the clinic,
and that model is reasonably predicted. What we've seen in
(33:58):
that is that real vergostama when it binds these two
targets on the same cell, produces better activity than when
you go just introduce a PD one and a tidget separately.
We've also seen that you know, the reduced FC function
that you've got with lvagostamig also seems to be differentiated
(34:23):
in that model compared to f C active modalities of data.
And then we just put that understanding of the mechanism
of action, understanding the level of t CUB proliferation, got
together with the emerging body of clinical data that we're
seeing in lung cancer, in billy tract cancer that you
refer to, in gastric cancer, habited cellular cancer, et cetera,
(34:46):
and we're building up a body of data that we
have that actually gives us confidence that first of all,
we're not seeing the enhanced side effects that sometimes seen
with other molecules that are in particular see active in
combination with chemotherapy regimens for example. Now you know, still
(35:06):
even the data that is out there with these with
these molecules, the adverse events aren't necessarily as high as
when you treat with a chemotherapy, but it's still causing
a discontinuation rate that may be affecting the long term
outcomes of patients on some of these trials. And so
we're encouraged by the fact we've got a very low
(35:27):
discontinuation rate for real vergostamik either as a monotherapy or
in combination with chemotherapy, or in combination with the ADCs,
So that's encouraging. Secondly, we are seeing you know, emerging
response rates, durability of response and landmark PFS rates, which
we find encouraging across the totality of the data. And
(35:49):
we think there's opportunity as well to further extend the
range of settings where you can get to an ADC
plus an IO that creates an opportunity to have a
differentiated red been compared with what's already out there. So
for all of those reasons, that's why we're investing behind
this molecule. I think there's there's opportunity.
Speaker 1 (36:07):
And yet, before I move on to a question for Dave,
I'm just going to take something you said that your
by specific is targeting molecules on the same cell. Is
that why you're not in PD one VEGEF and is
that why you're still excited by PD one or one four?
Speaker 3 (36:23):
So again, you know there's actually if you look at it,
there's quite a lot of data out there looking at
VEJEF added to io agents, right, And of course you
know when what we've done is look at those data
and see is this something that we can see that's
differentiated with the PD one vegeff by specifics compared with
what we'd see by adding a ved jeff targeted agent
(36:45):
to that background. And you know, and I would I
would just say that the jury remains out in that frame.
So if we look at the first line PDL one,
so first line nansmuscile lung cancer pedo one high group,
for example, we have data from the artmider One study
looking at real vogostamin and that setting where we've seen
(37:07):
you know, pfs and response rates in the same ballpark
as what's been described as well, So we think we've
got a competitive asset in that space. We've also got
an asset that we can combine with ved jeff as well,
and we've done that in the other cohorts of the
Gemini study. Obviously, exactly how that PFS benefit, which is impressive,
(37:28):
translates through to OS is still you know, a topic
for debate, And what we've seen typically across most of
the addition of veg jeff even onto an IO background,
is that you still get some deterioration of the effects
size between PFS and OS. We need to see exactly
what that that looks like. So you know, our approach is, look,
(37:49):
I think we can achieve much of this benefit by
adding a VEED Jeff directed agent into the regiments that
we're looking to do. And that's what that's what our
approach is.
Speaker 2 (37:59):
Okay.
Speaker 1 (37:59):
I think you've very consistent in saying that. So, Dave,
just thinking about the novelty of the Syriana six and
the innovativeness of the Syna six trial proof of concept
for ctDNA management guided therapy switch, do you expect continuing
to invest in using this kind of design going forward?
(38:20):
I mean, we saw the data at ASCO and you know,
so okay, some folks ask questions which we discussed earlier,
or does it depend on the ultimate outcome and the
uptake of this approach.
Speaker 4 (38:32):
Sim we certainly believe that blood based ctDNA guided decision
making will only increase as we move forward. I think
that in that regard, Serena six is a very exciting study,
not just because of what it represents for the patient
population that the study was designed for, but it creates
(38:53):
an opportunity for expanding the ambitions that we and the
field can have around how we can incorporate these types
of routine blood tests into the work that we need
to do to drive towards better outcomes. I think within
this context, we've got other studies that are looking to
(39:16):
incorporate ct DNA into the work that we're doing in
our own clinical trial settings. It's not it's it's it's
Susan could speak to this even better than I.
Speaker 5 (39:27):
It's not easy to do.
Speaker 4 (39:28):
We've we've tried this in in in lung cancer and
had to work through different assays and different ways of
of of of coming up with how we measure minimum
residual disease and other aspects with ct DNA. But I
do think more and more we will absolutely see this,
especially as we move into earlier settings where you know,
(39:50):
in metastatic or advanced disease SAM overall survival is the
gold standard and quite rightly what we in many instances
seek to pursue as we move into earlier stages of disease.
Speaker 5 (40:04):
To get to.
Speaker 4 (40:05):
Those overall survival endpoints requires a considerable amount of time
and large number of patients. In fact, being able to
have ct DNA MRD based approaches could very well represent
good surrogate opportunities as well for us to be advancing
medicines more quickly into patients that can benefit from them
(40:27):
straight away.
Speaker 1 (40:28):
I mean, I can think of a whole host of
things like I don't know, following cement emergence in an EGFR,
mutated patients while they're being treated, et cetera.
Speaker 2 (40:38):
Okay, and then Dave.
Speaker 1 (40:39):
Still with you, Destiny Bristol nine high cr rate long
stayble ow as tail. Dare I say, it suggests that
it's possible that some at a subset of her to
advance her to breast cancer patients can be dare I
say cured if that line stays flat, which is amazing.
(41:02):
Do you think you'd be able to identify these patients
and kind of what lessons did you learn from can
we take from the progress here to bring similar results
to other cancers.
Speaker 4 (41:12):
You talk about at the beginning of the podcast, some
of the changes that we've had a chance to witness
over the course of the last decade. I had the
great privilege and opportunity to work in the early days
on her septin, and I remember very very well when
we first had opportunities to show some of the adjuvant
(41:32):
data and the enthusiasm that we collectively felt for being
able to take a subtype of breast cancer that was
the worst prognosis and turn it into now a prognosis
that brought with it more hope for driving towards cure.
I have to say that the Destiny Bresto nine discussion
(41:55):
brought an equal sense of pride to me to be
able to hear from the podium belief that perhaps the
crs that we're looking with, if they remain durable over time,
start to introduce, as you just said, Sam, the possibility
of long term durable response and long term durable response
indeed could.
Speaker 6 (42:14):
Be cures today.
Speaker 4 (42:15):
I don't know that we have the opportunity to be
able to know which patients are likely to experience that response,
which is the reason, among others, why it's really important
for the best therapy to be used first. I think
that in breast cancer, one of the things I've observed
is that because there are a multitude of options that
(42:39):
are available to patients and the physicians who are treating them,
there can be I think, very thoughtful, but at times
perhaps a little academic discussions around sequencing and optimal approaches
towards thinking about therapies over time, and indeed that's very important,
But we do know time and time again that bringing
(43:01):
the best therapy first and upfront is oftentimes what results
in the best outcome for patients. And in this particular instance,
I think that we heard the community pretty unanimously clear
that the Destiny Breaston nine data with over forty months
of median pfs being presented, you compare to where we
(43:23):
were ten years ago, we were at four months, and
so just the progress that's been made over that and
with the complete response rates that we saw pretty breathtaking.
And remember one last important piece, over a third of
patients being treated for breast cancer in the frontline setting
of metastatic disease, unfortunately don't get an opportunity to see
(43:46):
a second line therapy, either because they progress, or they
pass away, or their performance status gets to a place
where they're not able to take therapy. So not only
are you moving the best therapy up front, but there
are more patients who can potentially benefit from that therapy
because you're in an earlier setting of the cancer.
Speaker 3 (44:06):
So, Susan, did you want to say something, well, just
that of course, one of the things we want to
then do is take that setting and learn about which
patients you know, potentially benefit. I do think this is
another setting where technologies like ctDNA can help inform the
patient individualized pathway through that. So we're going to have
(44:30):
to generate some of those data and understand that. And
I also think these trajectories of change that you can
put for an individual patient is also something that's suitable
for some of the AI modeling to approach and help
doing that. So I'm optimistic that we can take this
as a starting pact completely with Dave that right now,
this is the data that we have, and if it
were me, I'd want to have that best treatment at first.
(44:54):
But I think also we can study this and study
this setting and try and help inform over time, you know,
how you make some of those choices.
Speaker 1 (45:03):
And so actually, in an interesting related point, Susan or Dave,
one issue, if you want to call it that in
the study was the high proportion of denovo metastatic patients.
And I can't remember if it was you who brought
it up or the discussing or presenter. I can't find you.
I can't recall. Now this reflects a shifting obviously reality
(45:24):
in more patients. Again, that word cure and extended emissions.
Is this dynamic something that's likely to grow more common
with more effective agibate new agumant treatment. Going back to
something you said earlier, also, how do you track and
think about this and how do you think it will
impact how drugs are developed in the space because timelines
(45:45):
have become also quite large.
Speaker 3 (45:46):
Yeah, which is why some of these you know, intermediate
clinical endpoints can be really quite useful in doing that.
But you know, if we are successful in diagnosing more
cancers earlier, and we are successful in developing better NEWT
and perioperative regiments, then the expectation is that the percent
of those patients that then go on to despite adjuvant therapy,
(46:10):
despite surgery, et cetera, then progress is going to decrease.
And so you know, you would expect that over time
the proportion of patients in the first line metastatic that
our denovo will increase. So you know, again I think
in the current context, what I would say is, because
of the aging population around the world, the incidence of
(46:33):
cancer is still increasing. So whilst you know, even if
we're improving the cancer mortality rates, the total burden of
cancer is not decreasing yet. So you know for the
next you know, two to three decades, that demographic is
you know, that's built in, and so there will be
(46:55):
remaining plenty of opportunity if you like to treat patients
in both the early stage setup and in the metastic
setting for many of the cancers that were treating. But yes,
you know, as an overall trend, you'd expect the proportion
that our denovo to increase over time.
Speaker 4 (47:09):
Just on a very specific destiny breastone nine point. I
had an opportunity to hear many investigators comment that the
percentage of patients that were denovo and that study was
seen by them as a strength because in fact reflected
real world the patients that are presenting within their clinics
and within their hospitals, and that that is indeed a
(47:31):
patient population that they were keen to understand how the
treatment within her TOO and Producer map would be best
incorporated into that population.
Speaker 1 (47:41):
Right, we've got a few minutes left. Thank you Dave
for that, and thank you so far for all your insights.
I'm going to do some rapid fire questions. This one's
a thorny one, I think, I asked Susan at the
AACR pre event in April whether you'd sensed any tangible
change in your interactions with the FDA, and I think
you gave a very clear answer, no, has anything changed
(48:04):
since not yet?
Speaker 2 (48:07):
Okay, good, you see rapid fire.
Speaker 1 (48:09):
And have you felt any changes yet from the cuts
in an IH and the overall funding of science in
general in the US.
Speaker 3 (48:16):
Well, I just and this is not going to be
quite so quick. My view is that at the moment,
there's you know, an acceleration, as I said, in the
pace of innovation and in science. I just philosophically do
not feel that this is the moment which to back
off from investment in science, but actually to accelerate and
come behind it. That's what drives innovation in all of
(48:40):
the countries you know, around the world. Investment in the
science base, investment in the innovation or reward for innovation
you know, you know, delivers improvements and benefits for patients
and for those countries in terms of the world generations. So,
you know, philosophically, I think that's that's the approach that
that you know, we would support.
Speaker 2 (49:03):
But you haven't.
Speaker 1 (49:04):
I mean, I don't know where how long it takes
for these things to impact AstraZeneca because it's you know,
a lot of this is basic.
Speaker 3 (49:10):
Well, there's there's there's often you know, multiple years for
scientific you know, basic science discoveries to you know, flow
through into subsequent you know, often it comes through into
technological improvements that enable new discoveries, et cetera, et cetera.
So there's a there's a bit of a like time
on that. But again, you know, I would encourage all
(49:34):
countries that the investment in the science base and the
academic base is an important part, but also that needs
to be then you know, link linked to the innovation
and the investment in the life sciences sector, the enablement
of access to venture capital, et cetera, in order to
help companies start and strive and prosper. So all of
(49:57):
those things that I think important part of the ecosystem.
Speaker 1 (50:01):
Success, especially given I've got two kids who are trying
to be scientists. So I look forward to a positive
future for the Pascales often spoken about how impressed he's
been with science in China and drug development landscape. What
exactly changed over the past five to ten years.
Speaker 6 (50:18):
I can take a quick start.
Speaker 4 (50:20):
I think that one of the there's been several things
that have happened. One of the things that has happened
is that there's been really a modernization of Chinese FD eight,
and I think that the approval path has become much
more clear for medicines to be able to come to
market in China. Secondly, there's also been an important improvement
(50:43):
in the public payer modernization that's taking place. Still a
lot of progress that needs to be made there, but
more and more access being made. I'll let Susan speak
to some of the scientific elements, but the reason I
highlight those two dimensions is I think that, linking back
to your previous question, the US has led the life
(51:04):
sciences industry for decades, and I think that as a
result of that leadership position, there's been better access for
patients in the United States to innovative new medicines. There
has been greater number of clinical trials, and that the
time to public reimbursement for new and innovative medicines is
(51:29):
the shortest that it is across the globe. And I
think that in cancer in particular, we can see that
the outcomes have followed that, and so I think that
it's really really essential for countries that want to be
leaders in the life sciences space to ensure that they
are spending a fair share of their GDP on innovative medicines,
and that they are recognizing that that investment translates into
(51:53):
access and outcomes for patients. Let Susan speak maybe about
some of the other things she's seeing on the science
side within China, but I think those other dimensions are key.
Speaker 3 (52:02):
So I mean, China used to build on what David said,
has absolutely invested in the quality of the science at
the top universities over many years. And you see now
you said before, I think in terms of the citations
that there are many, you know, really very high quality
scientific publications that are coming in. They've also invested in
(52:25):
providing support, if you like, for their own life science companies.
They get support for sort of capital investment over a
period of time and support to access to funding. And
then also they've got reflux back into China of many
well trained scientists but with experience of working in the
(52:50):
West that has happened. And then with all of these
things together, they've very rapidly put that together into the
ability to actually create companies that can move at speed.
The other thing that's changed is the regulatory environment in China.
You know, five to ten years ago, it used to
take much longer in China to get a clinical trial open.
(53:11):
Now you can do it at the same speed in
China as you can in the US, or perhaps even
faster than you can in Europe. You know, So that
these things that are happening, and particularly the example in
the cell therapy area, which is one area where China
is actually leading in the innovation. They have this system
(53:31):
for allowing investigative initiated studies at single institutions that can
open very rapidly, and that allows you to iterate and
learn from the clinical stage of development very rapidly. And
that's why technologically and scientifically, you know, many Chinese companies
are at the leading edge in terms of the cell
(53:52):
therapy innovation. So I think it's just an example of
they've taken approach where saying this is something where we
want to be, you know, moving up the country ranking,
and they've taken a systematic approach to removing the barriers
to that and enabling the investment. You know, I think
(54:14):
that's a very similar approach that could be taken in Europe,
it could be taken in the in the US, and
just look at those areas where some of the barriers
can be removed and enable and unleash the innovation that
exists in all of these regions. There's no reason why
we can't do it, but you have to have the
will to do it and the will to think about,
(54:35):
you know, what those barriers are and how we can
improve on them. So my aspiration is that all areas
will look at, you know, how they can improve on
some of these and enable fast. You know, at the
end of the day, you know, it's cancer patients that
can benefit from some of the innovation that we've got
for and they haven't got the time to wait. So
(54:55):
I'm very enthusiastic about things that can help bring down
the barriers to drive in the innovation.
Speaker 1 (55:00):
I couldn't have wished for a better ending to a conversation,
to be honest with you, what maybe one last question
before I say goodbye, will there will there be an
eighth year of plenaries at ASCO.
Speaker 3 (55:11):
Well, Listen, I don't measure the success of the R
and D organization just solely on that metric. We're very
proud of what has been achieved already, but I think
the danger is for either complacency or said, look, you
know and that the ASCA plannary is always a highlight
because really shows things that are pushing the boundaries. If
(55:34):
we can possibly strive to do that again in the future,
I'd be absolutely delighted. But let's wait and see how
the Chians plan out.
Speaker 2 (55:42):
I look forward to.
Speaker 4 (55:43):
It, and you know, and Sam, right now, we really
stay focused in with those plannaries, just just just only
a few days behind us on making sure that those
plannarias result in approvals in reimbursement and that we're able
to get medicines to the patients who can benefit from them.
Speaker 6 (56:01):
That's what we stay focused on right now. In twenty
twenty five.
Speaker 1 (56:04):
Well, my fingers are cross for you and I'm really
excited to continue to watch very closely what do you
guys do. Thank you very much for taking time to
talk to me, Susan Dave. This has been an absolute pleasure,
and thank you. Let's see if you liked it, we
can try and do it again next year.
Speaker 3 (56:20):
Thank you very much.
Speaker 5 (56:20):
Thank you. Sam
Host
Jonathan Palmer
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