July 24, 2025 • 42 mins
“I like the label ‘new operating system.’ I think that does capture well what we're trying to do here,” says Dr. Ryan Schoenfeld, CEO of the Mark Foundation. In this episode of Vanguards of Health Care, Schoenfeld joins Bloomberg Intelligence analyst Sam Fazeli to explore how the foundation is redesigning cancer research through global collaboration, platform thinking and a bold portfolio approach. They discuss the Foundation’s growing international footprint, why basic research is increasingly under threat in the US, and where new breakthroughs — including solid tumor CAR-T and glioblastoma — may emerge in the next five years.
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Episode Transcript
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Speaker 1 (00:11):
Welcome everybody 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
san Faseli and I'm a pharmaceuticals analyst and head of
Global Industry Research at Bloomberg Intelligence, the in house research
arm of Bloomberg with five hundred analysts covering a whole
(00:33):
variety of sectors and asset classes. I'm thrilled to welcome
Ryan Schoenfeld, CEO of the Mark Foundation for Cancer Research.
Ryan is quietly building what could be described as I
hope he doesn't disagree with this, as a new operating
system for cancer research, applying the principles of venture strategy,
(00:56):
data driven decision making, and platform thinking to an industry
that really still is dominated by slow and for want
of a better phrase, siloed grant making. So the Mark
Foundation was founded in twenty seventeen by investor in philanthropist
Alex NaSTA, and it has already committed over two hundred
and fifty million dollars into a high risk, high reward
(01:19):
hopefully cancer research, with forty eight million dollars planned just
for twenty twenty five, although that my number might have changed.
I don't know, given what's happening in the US. So
welcome Ryan, Ryan. Can you give us some background on
your own career and what ultimately led you to join
the Mark Foundation and when, et cetera. Just give us
(01:39):
a bit of history.
Speaker 2 (01:40):
Absolutely. Sam. First, let me say how happy I am
to be here.
Speaker 3 (01:44):
I think this is a really a wonderful show that
you ran here, and I'm glad to be a part
of it. And thanks for the introduction. I like the
label new operating System. I think that's I think that
is something that does capture well what we're trying to
do here. My background is in pharmaceutical research. Initially, I
started my career following graduate school. I did a PhD
(02:08):
in synthetic organic chemistry began work as a medicinal chemist
at Roche. There used to be a research site in
California in the Bay Area, sadly which no longer exists.
It was a wonderful place to do research and I
started my career there. Was there for ten years, worked
on many different therapeutic areas. When that site closed, I
moved to the East Coast and worked for Roach's research
(02:30):
site in New Jersey. There I began to work more
on cancer. Oncology was one of the disease areas in
scope at that research site.
Speaker 2 (02:39):
And since I left.
Speaker 3 (02:40):
Roch about fifteen years ago, I have really expanded my
career in two directions.
Speaker 2 (02:45):
One in the nonprofit space.
Speaker 3 (02:48):
I initially left Roche to join a nonprofit that focused
on Huntington's disease research, which was very exciting, and also
data science. I spent about three and a half years
a Johnson and before I came to the Mark Foundation,
where I built and led a data science team working
implementing machine learning and AI solutions. This is going back
(03:09):
eleven years years ago to work on many different problems
in the pharmaceutical across the pharmaceutical value chain, from business
development to clinical operations, to commercial operations of course to
research as well, so focusing a lot of the time
on oncology, and since during the Mark Foundation a little
over seven years ago.
Speaker 2 (03:29):
Obviously focused full time on oncology.
Speaker 3 (03:31):
Now and what attracted me to come to the Mark
Foundation first and foremost is the mission. So the Mark
Foundation's mission is to accelerate new cancer therapeutics and new
diagnostics to move into the clinic it's a very translational emphasis,
where we're bridging the gap between exciting discoveries that are
made usually in academia, and getting those into exciting newly
(03:52):
discovered therapeutic candidates, diagnostics, et cetera that go into the clinic.
There's a lot of interesting science, exciting science that happens
during that journey, and there's there are funding gaps there.
Sometimes those gaps are filled by industry, but not always,
and an organization like the Mark Foundation can help fill
those important gaps to bring these important medicines and diagnostics
(04:14):
and tests to patients faster. And so that's what the
Mark Foundation is about. It's about speed, it's about risk,
it's about reward, it's about discovery. It's about translational research.
And when I met the founder you mentioned, Alex Master,
I was very impressed by his commitment to translational cancer
research and the way he'd set up the Mark Foundation,
setting it up actually as a public charity. So while
(04:35):
while we get much of our support still from our founder,
we also have other organizations and donors and private family
offices that have contributed to this cause as well.
Speaker 1 (04:49):
Great So, if you wanted to just perhaps lay out
your vision of the new operating system that let's let's
keep using that phrase that mass conduction is all.
Speaker 3 (05:01):
About absolutely, So it's about it's you know, it's about
two things. First, it's about collaboration, coalition building, partnership.
Speaker 2 (05:12):
On a global scale.
Speaker 3 (05:13):
So what we're looking for is our interested partners. And
these partners come from all sectors. So they come from
academia of course, that's our grant recipients. Typically they also
come from industry. We partner with biotech, with pharma, with venture,
with the investing side, and we also work with governments.
(05:34):
So we talked to and we will continue to seek
to partnerships with governments who supports basically anyone who's interested
in supporting cancer research around the world and working in
cancer research. So we have coalitions of funders that come together.
And then we also are a big believer in team science,
and we have coalitions of grantees of academic investigators, again
(05:56):
working across the globe. We're always trying to push push
the envelope of where, you know, where the exciting frontiers
are in research that if we if we didn't fund
this research today, that it probably wouldn't get funded because
it's too risky, or it's too early, or it's not
quite uh you know, ready for the currently existing funding
models wherever they may exist today. So we're always trying
(06:18):
to find find those opportunities, but of course make sure
that they still represent you know, the best ideas and
that we can see where they're going once what if
these if these high risk Kyroward research projects succeed, We
want to understand that this is in line with our
mission going to move the field forward, uh towards something
that will go to the clinic, uh for for cancer
(06:40):
patients to address an important gap.
Speaker 2 (06:41):
So that's the so that's the you know, that's the
coalition building.
Speaker 3 (06:46):
I think is the is is really the most important
part of this new operating model.
Speaker 2 (06:51):
And then the other the other aspect of that is
just it's still.
Speaker 3 (06:54):
A lot along the similar lines the way that we
look at research projects and the way that we consider
what is what we mean by risk. So we've created
a portfolio of research programs that span from you know,
small fellowship grants to one to two year grants to
test feasibility or proof of concept for an exciting new idea,
(07:15):
all the way to larger team science awards to fund
large groups of investigators to work together for multiple years.
And because we have this portfolio approach that we apply
across all cancer types, we can embrace this high risk
approach by taking this portfolio based approach where we can
Every year, we're funding maybe forty or so different projects
a year. Some are small, some are big, and you know,
(07:39):
some of them won't work because this is this is
cutting edge research, and we don't know what's going to happen.
But the ones that do work, we lean into them
and we you know, they can go seek funding elsewhere
if they're successful, but we can also move that forward.
Speaker 2 (07:51):
So we have a we have a programmatic.
Speaker 3 (07:54):
System that we build at the Mark Foundation to find
these project opportunities from around the world and also evaluate
them in a way that's both scientifically incredibly rigorous, but
also while being rigorous, embraces.
Speaker 2 (08:08):
Risk in a different way. So I think we have
a different.
Speaker 3 (08:10):
Way of looking at proposals and project opportunities than some
of the more you know, traditional long standing grant giving
programs that may exist out there in the world. So
those those are the two ways that our platform is embodied.
Speaker 1 (08:23):
Do they ryan do they always come to you? Or
do you have a search and evaluation platform of your own.
Speaker 2 (08:31):
We do both.
Speaker 3 (08:32):
So we have every year we have open calls for
proposals for a number of our programs. For our early
career support program called the Emerging Leader Award, for example,
every March we open a call for proposals. About every
year and a half or so, we have a call
for proposals for our Endeavor program, which is a Team
Science award, multi year, multimillion dollar Team Science award. And
(08:53):
with those two calls for proposals, they're open, you know,
to any investigator. The team side towards open globally the
early careers for us.
Speaker 2 (09:03):
In Canada, but we get a very nice, uh.
Speaker 3 (09:07):
Kind of sampling of of research topics across the cancer
research spectrum and we see what's going on. But we
also we have an internal scientific team that also works
very closely with our Scientific Advisory Committee and other other
valued members of our global cancer research network to always
try to brainstorm together and stay on top of where
(09:28):
we think, uh, there are emerging areas or areas that
that are poised for progress and a little bit of
funding could accelerate them through an inflection point on that way,
So with always kind of with a one year horizon.
We're thinking about new topics that we want to get into.
They could be disease focused, like recently we've done more
(09:49):
in glioblastoma. They could be mechanistically focused, like we had
a workshop last month on chromosomal instability. Uh and and
you know, and we had a we've had workshops recently
on earth detection for another example. And with these workshops,
so I mention I just mentioned workshops. We have a
workshop model where we three or four times a year,
(10:09):
we convene, you know, smaller intimate groups of investigators twenty
to thirty typically sometimes a little bit bigger, sometimes a
little smaller, for multiple days on one of these topics,
and then we will assign funding opportunities to people who
attended the workshop as well as sometimes we'll open the
calls for proposals up to the world, depending on the
(10:30):
topic and the nature of what we're doing. But this
is a proactive approach where we've identified a topic of interest,
we go out and we seek experts to come together
to one of these workshops. We intentionally curate these lists
so that they're not people who all already work together
and know each other some of them know each other,
some of them know some of each other, but not
everybody knows everyone of these things, and we hope that
(10:51):
by hosting these types of events, people will get together
and form new collaborations. This is what's been happening. We've
done about twelve of these so far, and that's the
definitely what happens coming out of these. And I think
the fact that we assign a grant giving opportunity to
these workshops really puts some action on the other side
of these meetings that we put together. We can fund
(11:12):
some some of the cool ideas to get presented at
these at these venues and collaborations to get struck up.
So that's that's one proactive way and another way we
just always with our internal scientific team, we're always trying
to keep our finger on the pulse of what's exciting,
going to conferences, reading the literature, and once in a
while when we see someone who has an amazing idea,
or we take a site visit to an institution, to
(11:34):
a cancer research center somewhere around the world and we
hear something amazing, we do have a process by which
we can consider, let's say, off cycle grant funding.
Speaker 2 (11:43):
So we do a little bit of that as well.
Speaker 1 (11:45):
So you did mention around the world. If you look
at your level of you know, the grants that you
give out or let's say your expenditure, call it that,
and how is it divided roughly US VERSUS Europe or
a US Europe China anyway.
Speaker 3 (12:01):
Yeah, yeah, So total grant funding to date since we
started the foundation in twenty seventeen to date is about
three quarters US one quarter outside the world. In recent years,
that's that ratio shifted a little bit to seventy thirty
or maybe two thirds one third US to x US.
And that's through just intentional scouting on our team's part
(12:25):
to go off and really we show up. We go
to meetings in Europe. We have good collaboration, We have
good conversations and connections and collaborations with folks around the world.
We have a number of grants that have gone out Europe, Israel, Australia.
We're excited when we see applications come in from other
parts of the world, and we're looking forward to continuing
(12:47):
to expand our global footprint of grantees.
Speaker 1 (12:50):
Right. So, while I'm on the subject, I'm going to
go on and talk about the what seems from a
distance at least a change in the ironment for basic
research and science in the US now, so the science base,
and I was really an interesting interview by Alison DeAngelis
at STAT in a publication that I'm sure you're familiar
(13:15):
with with somebody called Johannes Frauhalf who is the co
founder of labs Central and bio Labs, and there is
a venture capital business that he is also involved in,
and a few points came out of it that intrigued me,
including the fact that while both businesses seemed to be
doing okay and growing Farhaff said that there were already
(13:39):
cracks forming the articles comment he said he anticipated said
the industry will begin to feel the impact of grant
cuts from federal agencies right in earnest, by the end
of the year and early next year. As an example, again,
apparently people folks used to have to line up and
(13:59):
have a waiting list to get lab space. Now as
soon as there's somebody who wants something, So give us
your perspective on this, what are you seeing on the ground.
I've also then heard from the same conversation that actually
there are European for instance, universities going proactively. I don't
(14:20):
want to call it poaching, but pitching two US scientists.
But actually no real movements happening yet. But so give
us your understanding of it, because I think you're at
the code face right.
Speaker 3 (14:33):
We are, we are, and we work with a lot
of you know, I didn't mention earlier, but I'll say now,
we do work with a lot of startup venture stage companies,
some of whom we invest in and others of whom
have just they start with IP that comes out of
our grants, or just people in our network that are
that are starting companies. So we are very familiar with
the interface between academia and the venture startup landscape and cancer,
(14:55):
and so I saw one.
Speaker 2 (14:57):
I'll speak to a couple of trends. I'll answer.
Speaker 3 (15:00):
I'll come back to the question about about government funding
and where that where that could be having an impact.
So I'll start with a story that's a bit older.
If you think the last couple of years, especially in
maybe even three years, the funding landscape in venture for
venture stage companies, especially companies that are pre clinical stage
(15:21):
and seeking to enter the clinical stage, funding has become
very very difficult for those organizations to come up with
if they're not if they don't have a clinical development
plan that with the current rays that they're looking for
brings them to a clinical clinical efficacy endpoint. And then
they also need to have some convincing data to show
(15:43):
that they're going that the risk is low that they'll
get there. So companies venture stage companies that can show
all that get over subscribe roundstill, but those are very
few and far between. And what I think a lot
of the companies that used to populate or or would
be the clients of these incubators would be maybe more
platform based companies that are spinning out earlier that are
(16:05):
taking ideas from the academic setting for what could become
drug candidates but not drug candidates yet, and incubating them
in the private space with venture funding and eventually over
the course of a couple of years, moving those forward
into clinical candidates that then get further developed and eventually
a few years after that will show hopefully efficacy and
a patient population. So I think the venture landscape over
(16:30):
the last couple of years has been becoming more and
more risk averse, and I think that's starting to have
a that's starting to show its impact on what's happening
in the incubators as well right now, or just across
the whole landscape of startup companies. I think platform based
companies are having a hard time raising private capital if
they're not able to show that this rate, this money
(16:50):
will take them to the clinic and take them to
clinical efficacy. So that's one thing that I think is happening.
But the second thing, You're right, I think it's probably
too early to see the impact, but certainly in the
last six months we've seen a substantial cut to research
funding in the US, and by substantial I mean billions
of dollars that have been that have not gone into research,
(17:12):
and that's created sort of an atmosphere of uncertainty. I
think one reason to jump to your last question, one
reason why you probably haven't seen an exodus yet from
the US scientists are career scientists who work in academia.
This is a this is you know, people don't move around.
It's not like the in the company spaces where people
(17:32):
might move from one biotech to another one year to
the next.
Speaker 2 (17:35):
People who have labs in.
Speaker 3 (17:36):
An academic setting, it's a big, big thing to move
from one university to another, especially if it's in another country,
but even in the same country, that's a that's something
that people put one or two or three or more
years of thinking it too sometimes before they actually make
a move like that.
Speaker 2 (17:51):
So since it's we're.
Speaker 3 (17:52):
Only six months into this current environment of reduced funding
in the US, I think, you know, it may take
a little bit longer or to see if they're truly
is movement from the US institutions to abroad at the
investigator level. Now, at the postdoctoral level, that's already happening.
I think less postdocs are coming here, more postdocs are
(18:12):
are leaving sooner. So I think lab you know, the
staffing within labs in the US is starting to become
an issue. All this may lead to reduced output, and
I think also will ultimately if it's not already impacting.
I think the first reason I gave is probably a
bigger impact about why incubators may not be as full
this year as they were a couple of years ago
(18:32):
or a few years ago. But also the decreased amount
of academic research output you would expect from the reduced
funding will have an impact there. It's hard to say
exactly when and how much that impact will be and
when when it will hit. I think one interesting one
more point I'll just add to all this. I think
(18:53):
they're you know, reduced funding nationally here in the US
is probably going to hit basic fundamental research the hardest, especially,
you know, not just and we talk about in my field,
we talk about NIH budgets being reduced or being cut,
but NSF budgets have been cut as well or reduced
or you know, I'm less familiar with the details there,
but from what I've heard, there's been reductions and I
(19:14):
think basic research so the impact of that might not
we might not see that for ten years. But the
you know, if basic research, fundamental researches is less, then
the ideas that then become the translational research ideas to
become the platforms that ultimately produce the drug candidates. You'll
have a downstream effect that will maybe reduce the pipeline
(19:35):
of ideas to companies in the future.
Speaker 1 (19:40):
Right. So, and of course it doesn't really matter. I mean,
the quantum of money we're talking about needs quite a
few philanthropists to get together to try and replace. So
maybe if they end up listening to this, they all
start thinking about putting their money into organizations such as
yourselves to to try and make up some of the
(20:01):
pick up some of the slack. But that doesn't actually
matter to you where the science is at the end
of the day, if it ends up being that. I mean,
when I look at your stats, it looked like about
forty almost half of your funding didn't have a specific
tumor associated with it. It's if I assume that that
(20:21):
is basic research, then you know that's something in the
region of one hundred and twenty whatever a million dollars
that's gone into basic fundamental research if that assumption's correct.
So I'm assuming from your perspective it doesn't really change
anything as long as there's enough research happening somewhere, that's right.
Speaker 2 (20:41):
We look for the impact.
Speaker 3 (20:42):
We look to maximize the impact that the funding we
provide has, and so historically we've not looked at geography
that we've been acting. I mean, we've intentionally gone out
of a way to be you have to almost try
and not try in that way about geography. So since
we're based in the US, it we're naturally always easy
to bump into science in the US. We've done an
intentional job of looking elsewhere as well, And we're always
(21:05):
just looking for where if we didn't fund this today,
would this get funded? And you know, sometimes outside the
US that question, it's easier to say yes to that
because there are fewer government based funding opportunities in many
other countries.
Speaker 2 (21:20):
Outside the US.
Speaker 3 (21:21):
As the equation changes, if government funding becomes less available,
which is certainly seems to be the way things are
going here, you know, that may change the way we
look at some US based opportunities. We may look more favorably,
but we won't be looking at it just because it's
in the US or because it's in this country or
that country. We're just always going to continue I think
it's the right approach. We're always going to keep asking
(21:42):
ourselves if we didn't fund this research, would someone else
fund it? Should this research be funded? And if we
didn't fund it, who would fund it?
Speaker 2 (21:49):
Right?
Speaker 3 (21:49):
Those are questions that we're asking ourselves constantly. We're going
to keep asking that question, and you know, the inputs
may change, but the question won't change, and then whatever
whatever comes out the other side will be based on
our assessment of the answers to those questions. Always, we're
always going to be seeking to maximize the impact of
the funding that we provide towards accelerating exciting discoveries into
(22:13):
the clinic. And you did mention we have you know,
we're not tied to anyone cancer type of the Mark Foundation.
Speaker 2 (22:18):
So about half of our research projects cover.
Speaker 3 (22:22):
They typically some cover all cancer types because they're more
mechanistic and a little more fundamental in their nature. And
then some projects are would say multiple cancer types where
it's you know, it's something that it's still focused but
it's not necessarily focused on one very specific cancer. It's
focused on neuroendercrensumers, which cuts across a few different cancer
types or certain types of blood cancers, so leukemia's and
(22:45):
lymphoma's and my lomas right there are there are some
some areas so we we we range from focusing on
the very small, will even fund very rare cancer research
if we think that this funding will bring some bring
something through an inflection point, or we'll find research in
much more common cancer types. But there if we do,
(23:05):
the project that we're looking at needs to be something
that embodies some sort of risk in another way, you know,
whether it's bringing fields together like machine learning together with
cancer biology in a way that's new or doing something
that's not already being addressed elsewhere.
Speaker 1 (23:22):
I also wanted to get your before we move on
to more oncology focused conversation and your take on China.
The administration has its view on China, and it looks
like that they're making good progress on doing a possible
tariff or a trade deal, given some of the drum
beats that we hear about the rare els and the
(23:43):
access to chips, etc. But I've been going to the
region for the past twenty years and I have seen
a palpable change in the types of companies, going from
basically active ingredients for generics, to me too drug rugs,
to me better drugs, and now totally novel agents. It's
(24:05):
such that a lot of drugs that are coming out
of a region are being showing shown to be attractive
to US and European farmer companies. Now. One of the
things that I hear that that is really attractive about
the region is that they're much quicker to take a
concept to clinic and test it out, not by ignoring
(24:26):
ethics and patient safety, but just the amount of paperwork
is a lot less complicated. And then you've also got
the issue that there's a lot of variations on a
theme that are developed there, so you can kind of
pick from a menu almost. What is your perception how
(24:47):
much do you look at the region as a and
in general, Because at the end of the day, if
you're funding a grant where it's possible that it's going
to go into a phase one clinical trial, it sounds like,
assuming that people who want to fund it are able
to do that, they might be better to generate that
proof of concept trial in China or somewhere where the
(25:08):
speed with which you can recruit and do it and
calls is more attractive than in the US, although I
know there are efforts afoot to try and address them
in the US. To what's your perspective on.
Speaker 2 (25:19):
This, Yeah, to the last point.
Speaker 3 (25:21):
First, Yeah, I've heard the FDA's announced that they're going
to use AIM machine learning to try to make things.
Speaker 2 (25:29):
The process faster, and I hope that. I hope that
does work.
Speaker 3 (25:33):
I think for certain types of therapeutics, especially in the
cell engine therapy, their regulatory approach is more efficient and
expedient than ours is here now, especially on the GMP
side in terms of vector manufacturing and mixtures and things
like that that just lead to speed to clinic is
(25:55):
faster from a regulatory perspective. I think the other advantage
that they have right now, well, there's two others. One
you mentioned is cost cost or lower to run clinical
clinical development is the most expensive aspect of drug discovery.
The other the third is and this is also related
to cost, but it's it's it's time, the clinical operational effect.
You know, timelines are shorter there, they you know, site
(26:17):
efficiencies higher, they can enroll faster. Typically not all type
this is not this is more of a general statement.
I think for very specific cancer types. I don't know, uh,
you know, China may or may not be a place
where you'd see quicker enrollment, but in general you often
can see enrollment times in clinical trial site productivity be
higher in China. So so I think all those things
(26:39):
lead to reduce cost, more efficiency. I think it's still
a challenge for for drug developers outside of China to
look at you look and see how operations in China
running them at arm's length or trying to be there
on the ground, I think presents challenges. So I think
it's not a not an easy It's not an easy
(27:02):
answer for larger drug developers, I think in the smaller
biotech startup space there are The landscape is vast in
China and there are some amazing success stories in the
last few years. I mean legend was an example with
J and J going in and buying a China discovered
and developed drug for my loma a few years ago,
and that story.
Speaker 2 (27:22):
Will probably repeat.
Speaker 3 (27:23):
I spent a lot of time going to China, going back, yeah,
fifteen to twenty years when I was with Rosch and
later when I was with J and J, and so
I've seen on the scientific side, I mean, the culture
of science there is very strong. I've never seen, as
someone who spent the first half of my career as
an organic chemist working you know, working in connection with
(27:44):
the lab, I never saw so many organic chemists in
one place that as I saw when I would visit
Shanghai and Beijing and to go to different companies there.
So they have strength in terms of in terms of
their scientific capabilities.
Speaker 2 (27:59):
But I think, you know, it's not just China.
Speaker 3 (28:01):
You'll see Australia, for example, has a pretty forward looking
approach to regulatory in terms of cell therapy engine therapy.
So I think you're seeing people, you know, go in
Europe seems to be going in that direction as well too,
So I think the rest of the world is recognizing that,
you know, making clinical trial, clinical development more efficient, less
(28:23):
less costly is the way to go, and I think
you'll see that across the globe.
Speaker 1 (28:27):
Great, right, So let's go and talk about in the
last ten to fifteen minutes that we have together on
cology specifically, you're obviously at the cutting age, you have
your finger out. How many more different ways can I this?
Speaker 4 (28:39):
You have your finger on alls so and from outside
we of course see things when they kind of make
it to the clinic, and like the new modalities et
cetera that we're seeing, let's say, armored car ties, cartes
being designed through that method to be more act active
(29:00):
in solid tumors by specifics, clever cytokinds and you know,
and some of these, whether we believe it or not,
the data will continue to hopefully support that, some by
specifics that take two different mechanisms that are known but
seem to somehow bring some synergism some of the parts
(29:21):
is better than the individual. You know.
Speaker 1 (29:24):
We will find out this year whether VEGGIEFPD one by
specifics or tiget PD one by specific from our Zeneca
for example, genuinely make a difference to something that hadn't
worked so well as a as two single agents. But
so if you take all that, but if you look
at and put your crystal ball and look out five years,
(29:45):
what are the types of products ideas that we're going
to see that I should be at least teaching myself
the basic science on for when they come along.
Speaker 2 (29:57):
Well, I mean, I think more question.
Speaker 3 (30:00):
Yeah, yes, it's an exciting question though, I think, I mean,
I'll start with an area that I think you already
sound like you're pretty well up to speed on.
Speaker 2 (30:06):
But I think it's a it's an area that's still poised.
Speaker 3 (30:08):
It hasn't made a breakthrough yet despite all the efforts
for car TI for Solid tumor car TI for Solid Tumor,
has you know, we should be able to make this work.
Speaker 2 (30:19):
There's it's more.
Speaker 3 (30:20):
It's complicated, right, It's more complicated than the blood cancer setting.
The safety uh, you know considerations are certainly real, uh
and and we need to be careful with those. And
so armoring the cars up too much as a concern
not enough. They don't work. I think what the field
is poised for now is better understanding. This is gonna
this is being informed by real clinical data. What leads
(30:42):
to T cells the car te UH therapeutic modality itself
becoming more exhausted or starting off its life and a
place where it's going to be more prone to become exhausted.
So there's all kinds of concepts kind of baked into that,
going from the relationships with aging and cancer and so
in an age population where it's an atologous process and
so the immune cells have have you know, have an
(31:04):
aging component that we still need to understand more about,
and then we can if we understand what's making those
cells you know old, let's say, for lack of a
better word, we can we can help, you know, in
the x VVO process, rejuvenate them or in the or
put more energy into the alogenetic process, because we feel
like that's going to be the only thing that solves.
Speaker 2 (31:23):
The problem, you know.
Speaker 3 (31:24):
So we're working on answers for that, and I think
we'll see the car TI field for solid tumor hopefully
make some breakthroughs in the next you know, so by
five years from now, look at my crystal ball. I
think we'll have seen safe and efficacious cartes for solid
tumors and at least a couple of different indications, ideally
a pediatric and adult. One place I'm really excited to
(31:45):
see this progress is in glioblastoma, which is a disease
that's been you know, has not really had a therapeutic
breakthrough in over twenty years since timazolamide, more than twenty years.
So the car T cells showed some promise, but it's
not really durable, so we need to understand how to
keep those cells working for longer. But at least we
know there's some good targets in there now, which is encouraging.
(32:07):
And so you're going to see people working on those
targets and souping up their carte cells and trying to
get you know, deliveries and extra challenge getting things into
the brain that need to be there at the right levels,
et cetera, and the right combinations.
Speaker 2 (32:19):
Maybe even so so, but.
Speaker 3 (32:20):
I'm I'm uh, I'm excited about the next five years
in gliablastoma research. I think that field has been you know,
very long overdue for a breakthrough.
Speaker 2 (32:28):
I'd love to see what happen.
Speaker 3 (32:29):
It's such a you know, the the unmet need there
is so high. So that's so that's that's one area.
The other area you mentioned, you mentioned combinations. You mentioned
some really exciting by specific combinations, two different mechanisms on
one drug. That's you know, the famous you know, the
last year or so, the veg FPD one's got a
lot of attention digit PD one. Looking forward to seeing
how that plays out. I think understanding combination approaches better generally.
(32:54):
It's not a it's not a new concept that we
want to combine drugs, but I still think the cancer field.
As someone who worked in virology earlier in my career,
I feel like we were more successful and that was
maybe you could argue was technically easier, but HIV HTV.
We were able to bring these cocktails of combinations to
bear earlier in a way that prevented the prevented you know,
(33:18):
really worked for patients in a robust, durable way and
prevented the viruses from escaping. Let's say, right, so can
we do the same for cancer. I think the opportunity
for cancer to tie this back into something that's a
little more forward looking. I think we'll come in the
earlier treatment setting so we can get better early detection,
which is a diagnostic problem that we're still working on.
(33:39):
And then define a patient population in whom we can
practice disease interception now and treat patients earlier instead of
waiting till they're advanced or we detected later. In treating
metastatic disease, treat patients in an earlier setting, at earlier
stage or even pre cancer where we know the risk
is high enough to warrant treatment still, and use combination
(34:00):
to really just stop that, stop that cancer progression cold
in its tracks.
Speaker 2 (34:05):
Before it really ever gets started.
Speaker 3 (34:06):
So I think the next five years this kind of
intersection between early detection, disease interception, and therapeutic understanding of
how combinations and different agents can work together. Hopefully we'll
all converge to reduce cancer mortality. And I think the
early detection field is going to need that. So early
detection we can detect cancers earlier. But what do we
do about it? Does that really matter? Does ultimately does
(34:27):
that benefit patients? I think the only way you get
to a yes for that is if you can improve
your ability to intercept disease sooner or treat it sooner,
treat it earlier, and you'll need different drug combinations for that.
Speaker 1 (34:38):
Yeah. Yeah, you need to have one of your workshops,
need to be with insurance companies going forward, trying to
convince them that it's a good idea to prevent disease
then treat patients in the last life.
Speaker 2 (34:49):
Yeah.
Speaker 1 (34:50):
So one of the I'm going to do a little
lightning round type thing. I like the idea. Pretty much
every podcast has got one, you know, I thought we
might this, but before I get there is an example
that's just evolving right now, which is smoldering multiple my looma,
which is the it's not quite m gast. It's not
that very first spike in in monoclonal demopathies or anything
(35:15):
it is. But I mean, there are physicians who believe
it's a cancer, except it's not symptomatic yet. So and
we've just seen a trial read out for a single drug, Darzalex,
that's shown significant benefit in terms of prevention of it
to become symptomatic multiple my looma, And there, I think
(35:36):
is actually doable. We don't even need to do anything
new because you do the blood tests and you're there already,
so let's hope that other cancers can catch up with it.
You know, I'd love the idea of being able to
go in a big PET scan or CT scanner. Here
you go, you've got a two centimeter one centimeter thing
in your lung. It might not be cancer, or we're
(35:57):
just going to treat it for now, see what it happens.
Speaker 3 (35:59):
Right, So, okay, this is by way, that's exactly what
I'm talking about.
Speaker 2 (36:03):
Exactly.
Speaker 3 (36:03):
That's the disease interception, is exactly identifying those pre cancer
states that you could debate semantically whether or not you
even call them cancer, but still they're treatable and understanding
how to treat them.
Speaker 2 (36:15):
I'm very excited.
Speaker 1 (36:16):
Oh but you're I think our biggest challenge is going
to be with the payers and also the former companies,
because you're gonna end up with a much larger patient population.
They need to have to figure out whether how their
pricing structure works. So there's quite a lot of work
to be done there. Right, very quick, was we've got
about five five minutes, six minutes left and next big
jump in survival which tumor will that be? So let
(36:38):
me give you examples. We've had my Looma. We've had melanoma.
Breast cancer is pretty much you know, I mean, unfortunately,
there are still people who get caught too late for
the wrong reasons. But let's say it's relatively under control,
and we'll just keep what's the next one? Where is
your biggest where is your white hope? And I'm gonna
give you some leaders pank creative cleoma, kidney, Well.
Speaker 2 (37:00):
That's where the UNMETT need is the highest.
Speaker 3 (37:01):
In pancreas and glioma for sure, that's where the I
mean and ovarian I I would say the next big change, Well,
it's already here a little bit. So I'm gonna maybe
maybe maybe this answer is just sort of a I
hope it's not a cop out.
Speaker 2 (37:15):
But I think treating MSI high, if we're figuring out.
Speaker 3 (37:19):
A way that that I never saw a response, I mean,
the response rates that that we've seen in that trial
one hundred percent, right, they're amazing. So extending that to
all the cancers types to which that will apply at
at scale, because that hasn't really rolled out to the
proper population at large, I think people are MSI high
is always now a candidate for for checkpoint. But I
think you'll see that rolled out in a more intentional way.
You can see a lot of live stave. So it's
(37:40):
a cop out because it's not it's not one cancer type,
it's a it's a signature across multiple cancers.
Speaker 2 (37:44):
But you're going to see I'll take that.
Speaker 3 (37:46):
Yeah, So I think that's where you're gonna see in
the short term the biggest benefit to you know, uh,
to cancer patients in the short term. But okay, so
the longer term, I'm hopeful for gleablastoma and pancreas, but
I think those are still very hard and we've.
Speaker 1 (37:58):
Seen some really good cartida there. Yeah, I guess crossed
it would replicate. Now I'm going to end with AI
type questions hype versus real, you know, give the give us,
but we need to be quick here. Impact of AI
on biology and understanding basic biology hype or real hype? Okay,
(38:19):
Impact of AI on the basic steps of drug discovery,
designing molecules, designing clever antibodies, clever enzymes, et cetera. Hyper real, real,
impact on clinical trial design and klick trial conduct, real filing.
Speaker 3 (38:36):
Should be should be real real, I think that, But
certainly AI technology is ready to do that real and
whether it's actually happening or not yet, I'm not sure
it is, but but the technology AI technology is where
it should be to do.
Speaker 1 (38:47):
That, and then taking it to that stage that we've
kind of started with finding patients, finding them early, treating them.
Speaker 3 (38:54):
Early real I mean, I mean between hype and real,
go real.
Speaker 2 (38:58):
But there's a lot more work to be done to
implement that.
Speaker 3 (39:00):
I think machine learning has has brought early detection forward,
has really helped make early detection much better, but then
there's so many other challenges to make early detection translate
into better patient outcomes.
Speaker 1 (39:10):
Now, just as a matter of interest, I've just listened
to a podcast from knee Gium AI and they had
a conversation about this company that's just spun out of
Flagship VC that is trying to create an agentic AI
that comes up with hypothesis. I think that's what I
understood them say, comes up with the hypothesis, can actually
run the lab and test it and then refine his experiment.
(39:33):
That's what they're working on. So maybe biology will become
at least some form of reality at some point, But
I think.
Speaker 2 (39:40):
Yeah, type now, but it could become real. I definitely.
Speaker 3 (39:42):
I definitely wouldn't say I bulsh about the future for
biology for sure. For that I agree brilliantly.
Speaker 1 (39:48):
No, no, no, But that was interesting because I think
it's one of the first times I've heard it. I
know biontake through their one of their AI subsidiary that
they own, they have thought about talked about automated completely
in the box. Ultimately, Yeah, let's see.
Speaker 3 (40:03):
You could you could? You could imagine that for for sure.
I think I think the first thing AI should be
it has been applied and I think could be extended
to just inform experimental design better. Right understanding, we can
we can answer the questions with fewer experiments and using
AI to do that. Well, it is something that's that's real,
that's not hype, and that's that's here today. And I
think those principles will become as they feed into the
(40:26):
agentic approaches will then in the in the closed loop
you'll see that.
Speaker 2 (40:30):
But but we'll see.
Speaker 1 (40:30):
What Ryan, We've got a minute left. How would you
like to sign off?
Speaker 3 (40:34):
Well, I would just like to say, well, first of all, Sam,
I've enjoyed I've enjoyed speaking with you. Try this has
been a lot of fun. I would like to sign
off optimistically. I would like to say that I I
am truly inspired by how much how scientists and funding organizations, industry,
government really all do want to work together, uh in
(40:57):
ways to address the problems that face so many of
our friends and family that we've we've all been touched
by cancer someone we know. I mean, just it's such
a you know, it's such a prevalent condition. And as
the human population, you know, as longevity increases and aging increases,
I think cancer will continue to increase as much as
we're treating it.
Speaker 2 (41:18):
More effectively in some settings.
Speaker 3 (41:19):
So I'm very inspired by how how much the field
wants to come together and how much people enjoy working together.
So we're happy to you know, the Mark Foundation for
Cancer Research is happy to play our part in that
and to be a facilitator and a coalition builder bringing
scientists and like minded organizations together to uh to really
uh move uh move move science forward and bring deliver
(41:43):
new uh new drugs and new diagnostics for patients.
Speaker 1 (41:47):
That's brilliant. Thank you very much, Ryan Ranchelfed, CEO of
Mark the Mark Foundation, thank you for the good work
that you do. Is pretty clear that you that it
gives you a lot of energy doing this, so we
appreciate it, and I look forward to being invited to
some of your workshops and be a flyer all and maybe.
Speaker 2 (42:04):
Learn something absolutely absolutely.
Speaker 1 (42:07):
Thank you very much and speak to you soon. M
h m m
Welcome everybody 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
san Faseli and I'm a pharmaceuticals analyst and head of
Global Industry Research at Bloomberg Intelligence, the in house research
arm of Bloomberg with five hundred analysts covering a whole
(00:33):
variety of sectors and asset classes. I'm thrilled to welcome
Ryan Schoenfeld, CEO of the Mark Foundation for Cancer Research.
Ryan is quietly building what could be described as I
hope he doesn't disagree with this, as a new operating
system for cancer research, applying the principles of venture strategy,
(00:56):
data driven decision making, and platform thinking to an industry
that really still is dominated by slow and for want
of a better phrase, siloed grant making. So the Mark
Foundation was founded in twenty seventeen by investor in philanthropist
Alex NaSTA, and it has already committed over two hundred
and fifty million dollars into a high risk, high reward
(01:19):
hopefully cancer research, with forty eight million dollars planned just
for twenty twenty five, although that my number might have changed.
I don't know, given what's happening in the US. So
welcome Ryan, Ryan. Can you give us some background on
your own career and what ultimately led you to join
the Mark Foundation and when, et cetera. Just give us
(01:39):
a bit of history.
Speaker 2 (01:40):
Absolutely. Sam. First, let me say how happy I am
to be here.
Speaker 3 (01:44):
I think this is a really a wonderful show that
you ran here, and I'm glad to be a part
of it. And thanks for the introduction. I like the
label new operating System. I think that's I think that
is something that does capture well what we're trying to
do here. My background is in pharmaceutical research. Initially, I
started my career following graduate school. I did a PhD
(02:08):
in synthetic organic chemistry began work as a medicinal chemist
at Roche. There used to be a research site in
California in the Bay Area, sadly which no longer exists.
It was a wonderful place to do research and I
started my career there. Was there for ten years, worked
on many different therapeutic areas. When that site closed, I
moved to the East Coast and worked for Roach's research
(02:30):
site in New Jersey. There I began to work more
on cancer. Oncology was one of the disease areas in
scope at that research site.
Speaker 2 (02:39):
And since I left.
Speaker 3 (02:40):
Roch about fifteen years ago, I have really expanded my
career in two directions.
Speaker 2 (02:45):
One in the nonprofit space.
Speaker 3 (02:48):
I initially left Roche to join a nonprofit that focused
on Huntington's disease research, which was very exciting, and also
data science. I spent about three and a half years
a Johnson and before I came to the Mark Foundation,
where I built and led a data science team working
implementing machine learning and AI solutions. This is going back
(03:09):
eleven years years ago to work on many different problems
in the pharmaceutical across the pharmaceutical value chain, from business
development to clinical operations, to commercial operations of course to
research as well, so focusing a lot of the time
on oncology, and since during the Mark Foundation a little
over seven years ago.
Speaker 2 (03:29):
Obviously focused full time on oncology.
Speaker 3 (03:31):
Now and what attracted me to come to the Mark
Foundation first and foremost is the mission. So the Mark
Foundation's mission is to accelerate new cancer therapeutics and new
diagnostics to move into the clinic it's a very translational emphasis,
where we're bridging the gap between exciting discoveries that are
made usually in academia, and getting those into exciting newly
(03:52):
discovered therapeutic candidates, diagnostics, et cetera that go into the clinic.
There's a lot of interesting science, exciting science that happens
during that journey, and there's there are funding gaps there.
Sometimes those gaps are filled by industry, but not always,
and an organization like the Mark Foundation can help fill
those important gaps to bring these important medicines and diagnostics
(04:14):
and tests to patients faster. And so that's what the
Mark Foundation is about. It's about speed, it's about risk,
it's about reward, it's about discovery. It's about translational research.
And when I met the founder you mentioned, Alex Master,
I was very impressed by his commitment to translational cancer
research and the way he'd set up the Mark Foundation,
setting it up actually as a public charity. So while
(04:35):
while we get much of our support still from our founder,
we also have other organizations and donors and private family
offices that have contributed to this cause as well.
Speaker 1 (04:49):
Great So, if you wanted to just perhaps lay out
your vision of the new operating system that let's let's
keep using that phrase that mass conduction is all.
Speaker 3 (05:01):
About absolutely, So it's about it's you know, it's about
two things. First, it's about collaboration, coalition building, partnership.
Speaker 2 (05:12):
On a global scale.
Speaker 3 (05:13):
So what we're looking for is our interested partners. And
these partners come from all sectors. So they come from
academia of course, that's our grant recipients. Typically they also
come from industry. We partner with biotech, with pharma, with venture,
with the investing side, and we also work with governments.
(05:34):
So we talked to and we will continue to seek
to partnerships with governments who supports basically anyone who's interested
in supporting cancer research around the world and working in
cancer research. So we have coalitions of funders that come together.
And then we also are a big believer in team science,
and we have coalitions of grantees of academic investigators, again
(05:56):
working across the globe. We're always trying to push push
the envelope of where, you know, where the exciting frontiers
are in research that if we if we didn't fund
this research today, that it probably wouldn't get funded because
it's too risky, or it's too early, or it's not
quite uh you know, ready for the currently existing funding
models wherever they may exist today. So we're always trying
(06:18):
to find find those opportunities, but of course make sure
that they still represent you know, the best ideas and
that we can see where they're going once what if
these if these high risk Kyroward research projects succeed, We
want to understand that this is in line with our
mission going to move the field forward, uh towards something
that will go to the clinic, uh for for cancer
(06:40):
patients to address an important gap.
Speaker 2 (06:41):
So that's the so that's the you know, that's the
coalition building.
Speaker 3 (06:46):
I think is the is is really the most important
part of this new operating model.
Speaker 2 (06:51):
And then the other the other aspect of that is
just it's still.
Speaker 3 (06:54):
A lot along the similar lines the way that we
look at research projects and the way that we consider
what is what we mean by risk. So we've created
a portfolio of research programs that span from you know,
small fellowship grants to one to two year grants to
test feasibility or proof of concept for an exciting new idea,
(07:15):
all the way to larger team science awards to fund
large groups of investigators to work together for multiple years.
And because we have this portfolio approach that we apply
across all cancer types, we can embrace this high risk
approach by taking this portfolio based approach where we can
Every year, we're funding maybe forty or so different projects
a year. Some are small, some are big, and you know,
(07:39):
some of them won't work because this is this is
cutting edge research, and we don't know what's going to happen.
But the ones that do work, we lean into them
and we you know, they can go seek funding elsewhere
if they're successful, but we can also move that forward.
Speaker 2 (07:51):
So we have a we have a programmatic.
Speaker 3 (07:54):
System that we build at the Mark Foundation to find
these project opportunities from around the world and also evaluate
them in a way that's both scientifically incredibly rigorous, but
also while being rigorous, embraces.
Speaker 2 (08:08):
Risk in a different way. So I think we have
a different.
Speaker 3 (08:10):
Way of looking at proposals and project opportunities than some
of the more you know, traditional long standing grant giving
programs that may exist out there in the world. So
those those are the two ways that our platform is embodied.
Speaker 1 (08:23):
Do they ryan do they always come to you? Or
do you have a search and evaluation platform of your own.
Speaker 2 (08:31):
We do both.
Speaker 3 (08:32):
So we have every year we have open calls for
proposals for a number of our programs. For our early
career support program called the Emerging Leader Award, for example,
every March we open a call for proposals. About every
year and a half or so, we have a call
for proposals for our Endeavor program, which is a Team
Science award, multi year, multimillion dollar Team Science award. And
(08:53):
with those two calls for proposals, they're open, you know,
to any investigator. The team side towards open globally the
early careers for us.
Speaker 2 (09:03):
In Canada, but we get a very nice, uh.
Speaker 3 (09:07):
Kind of sampling of of research topics across the cancer
research spectrum and we see what's going on. But we
also we have an internal scientific team that also works
very closely with our Scientific Advisory Committee and other other
valued members of our global cancer research network to always
try to brainstorm together and stay on top of where
(09:28):
we think, uh, there are emerging areas or areas that
that are poised for progress and a little bit of
funding could accelerate them through an inflection point on that way,
So with always kind of with a one year horizon.
We're thinking about new topics that we want to get into.
They could be disease focused, like recently we've done more
(09:49):
in glioblastoma. They could be mechanistically focused, like we had
a workshop last month on chromosomal instability. Uh and and
you know, and we had a we've had workshops recently
on earth detection for another example. And with these workshops,
so I mention I just mentioned workshops. We have a
workshop model where we three or four times a year,
(10:09):
we convene, you know, smaller intimate groups of investigators twenty
to thirty typically sometimes a little bit bigger, sometimes a
little smaller, for multiple days on one of these topics,
and then we will assign funding opportunities to people who
attended the workshop as well as sometimes we'll open the
calls for proposals up to the world, depending on the
(10:30):
topic and the nature of what we're doing. But this
is a proactive approach where we've identified a topic of interest,
we go out and we seek experts to come together
to one of these workshops. We intentionally curate these lists
so that they're not people who all already work together
and know each other some of them know each other,
some of them know some of each other, but not
everybody knows everyone of these things, and we hope that
(10:51):
by hosting these types of events, people will get together
and form new collaborations. This is what's been happening. We've
done about twelve of these so far, and that's the
definitely what happens coming out of these. And I think
the fact that we assign a grant giving opportunity to
these workshops really puts some action on the other side
of these meetings that we put together. We can fund
(11:12):
some some of the cool ideas to get presented at
these at these venues and collaborations to get struck up.
So that's that's one proactive way and another way we
just always with our internal scientific team, we're always trying
to keep our finger on the pulse of what's exciting,
going to conferences, reading the literature, and once in a
while when we see someone who has an amazing idea,
or we take a site visit to an institution, to
(11:34):
a cancer research center somewhere around the world and we
hear something amazing, we do have a process by which
we can consider, let's say, off cycle grant funding.
Speaker 2 (11:43):
So we do a little bit of that as well.
Speaker 1 (11:45):
So you did mention around the world. If you look
at your level of you know, the grants that you
give out or let's say your expenditure, call it that,
and how is it divided roughly US VERSUS Europe or
a US Europe China anyway.
Speaker 3 (12:01):
Yeah, yeah, So total grant funding to date since we
started the foundation in twenty seventeen to date is about
three quarters US one quarter outside the world. In recent years,
that's that ratio shifted a little bit to seventy thirty
or maybe two thirds one third US to x US.
And that's through just intentional scouting on our team's part
(12:25):
to go off and really we show up. We go
to meetings in Europe. We have good collaboration, We have
good conversations and connections and collaborations with folks around the world.
We have a number of grants that have gone out Europe, Israel, Australia.
We're excited when we see applications come in from other
parts of the world, and we're looking forward to continuing
(12:47):
to expand our global footprint of grantees.
Speaker 1 (12:50):
Right. So, while I'm on the subject, I'm going to
go on and talk about the what seems from a
distance at least a change in the ironment for basic
research and science in the US now, so the science base,
and I was really an interesting interview by Alison DeAngelis
at STAT in a publication that I'm sure you're familiar
(13:15):
with with somebody called Johannes Frauhalf who is the co
founder of labs Central and bio Labs, and there is
a venture capital business that he is also involved in,
and a few points came out of it that intrigued me,
including the fact that while both businesses seemed to be
doing okay and growing Farhaff said that there were already
(13:39):
cracks forming the articles comment he said he anticipated said
the industry will begin to feel the impact of grant
cuts from federal agencies right in earnest, by the end
of the year and early next year. As an example, again,
apparently people folks used to have to line up and
(13:59):
have a waiting list to get lab space. Now as
soon as there's somebody who wants something, So give us
your perspective on this, what are you seeing on the ground.
I've also then heard from the same conversation that actually
there are European for instance, universities going proactively. I don't
(14:20):
want to call it poaching, but pitching two US scientists.
But actually no real movements happening yet. But so give
us your understanding of it, because I think you're at
the code face right.
Speaker 3 (14:33):
We are, we are, and we work with a lot
of you know, I didn't mention earlier, but I'll say now,
we do work with a lot of startup venture stage companies,
some of whom we invest in and others of whom
have just they start with IP that comes out of
our grants, or just people in our network that are
that are starting companies. So we are very familiar with
the interface between academia and the venture startup landscape and cancer,
(14:55):
and so I saw one.
Speaker 2 (14:57):
I'll speak to a couple of trends. I'll answer.
Speaker 3 (15:00):
I'll come back to the question about about government funding
and where that where that could be having an impact.
So I'll start with a story that's a bit older.
If you think the last couple of years, especially in
maybe even three years, the funding landscape in venture for
venture stage companies, especially companies that are pre clinical stage
(15:21):
and seeking to enter the clinical stage, funding has become
very very difficult for those organizations to come up with
if they're not if they don't have a clinical development
plan that with the current rays that they're looking for
brings them to a clinical clinical efficacy endpoint. And then
they also need to have some convincing data to show
(15:43):
that they're going that the risk is low that they'll
get there. So companies venture stage companies that can show
all that get over subscribe roundstill, but those are very
few and far between. And what I think a lot
of the companies that used to populate or or would
be the clients of these incubators would be maybe more
platform based companies that are spinning out earlier that are
(16:05):
taking ideas from the academic setting for what could become
drug candidates but not drug candidates yet, and incubating them
in the private space with venture funding and eventually over
the course of a couple of years, moving those forward
into clinical candidates that then get further developed and eventually
a few years after that will show hopefully efficacy and
a patient population. So I think the venture landscape over
(16:30):
the last couple of years has been becoming more and
more risk averse, and I think that's starting to have
a that's starting to show its impact on what's happening
in the incubators as well right now, or just across
the whole landscape of startup companies. I think platform based
companies are having a hard time raising private capital if
they're not able to show that this rate, this money
(16:50):
will take them to the clinic and take them to
clinical efficacy. So that's one thing that I think is happening.
But the second thing, You're right, I think it's probably
too early to see the impact, but certainly in the
last six months we've seen a substantial cut to research
funding in the US, and by substantial I mean billions
of dollars that have been that have not gone into research,
(17:12):
and that's created sort of an atmosphere of uncertainty. I
think one reason to jump to your last question, one
reason why you probably haven't seen an exodus yet from
the US scientists are career scientists who work in academia.
This is a this is you know, people don't move around.
It's not like the in the company spaces where people
(17:32):
might move from one biotech to another one year to
the next.
Speaker 2 (17:35):
People who have labs in.
Speaker 3 (17:36):
An academic setting, it's a big, big thing to move
from one university to another, especially if it's in another country,
but even in the same country, that's a that's something
that people put one or two or three or more
years of thinking it too sometimes before they actually make
a move like that.
Speaker 2 (17:51):
So since it's we're.
Speaker 3 (17:52):
Only six months into this current environment of reduced funding
in the US, I think, you know, it may take
a little bit longer or to see if they're truly
is movement from the US institutions to abroad at the
investigator level. Now, at the postdoctoral level, that's already happening.
I think less postdocs are coming here, more postdocs are
(18:12):
are leaving sooner. So I think lab you know, the
staffing within labs in the US is starting to become
an issue. All this may lead to reduced output, and
I think also will ultimately if it's not already impacting.
I think the first reason I gave is probably a
bigger impact about why incubators may not be as full
this year as they were a couple of years ago
(18:32):
or a few years ago. But also the decreased amount
of academic research output you would expect from the reduced
funding will have an impact there. It's hard to say
exactly when and how much that impact will be and
when when it will hit. I think one interesting one
more point I'll just add to all this. I think
(18:53):
they're you know, reduced funding nationally here in the US
is probably going to hit basic fundamental research the hardest, especially,
you know, not just and we talk about in my field,
we talk about NIH budgets being reduced or being cut,
but NSF budgets have been cut as well or reduced
or you know, I'm less familiar with the details there,
but from what I've heard, there's been reductions and I
(19:14):
think basic research so the impact of that might not
we might not see that for ten years. But the
you know, if basic research, fundamental researches is less, then
the ideas that then become the translational research ideas to
become the platforms that ultimately produce the drug candidates. You'll
have a downstream effect that will maybe reduce the pipeline
(19:35):
of ideas to companies in the future.
Speaker 1 (19:40):
Right. So, and of course it doesn't really matter. I mean,
the quantum of money we're talking about needs quite a
few philanthropists to get together to try and replace. So
maybe if they end up listening to this, they all
start thinking about putting their money into organizations such as
yourselves to to try and make up some of the
(20:01):
pick up some of the slack. But that doesn't actually
matter to you where the science is at the end
of the day, if it ends up being that. I mean,
when I look at your stats, it looked like about
forty almost half of your funding didn't have a specific
tumor associated with it. It's if I assume that that
(20:21):
is basic research, then you know that's something in the
region of one hundred and twenty whatever a million dollars
that's gone into basic fundamental research if that assumption's correct.
So I'm assuming from your perspective it doesn't really change
anything as long as there's enough research happening somewhere, that's right.
Speaker 2 (20:41):
We look for the impact.
Speaker 3 (20:42):
We look to maximize the impact that the funding we
provide has, and so historically we've not looked at geography
that we've been acting. I mean, we've intentionally gone out
of a way to be you have to almost try
and not try in that way about geography. So since
we're based in the US, it we're naturally always easy
to bump into science in the US. We've done an
intentional job of looking elsewhere as well, And we're always
(21:05):
just looking for where if we didn't fund this today,
would this get funded? And you know, sometimes outside the
US that question, it's easier to say yes to that
because there are fewer government based funding opportunities in many
other countries.
Speaker 2 (21:20):
Outside the US.
Speaker 3 (21:21):
As the equation changes, if government funding becomes less available,
which is certainly seems to be the way things are
going here, you know, that may change the way we
look at some US based opportunities. We may look more favorably,
but we won't be looking at it just because it's
in the US or because it's in this country or
that country. We're just always going to continue I think
it's the right approach. We're always going to keep asking
(21:42):
ourselves if we didn't fund this research, would someone else
fund it? Should this research be funded? And if we
didn't fund it, who would fund it?
Speaker 2 (21:49):
Right?
Speaker 3 (21:49):
Those are questions that we're asking ourselves constantly. We're going
to keep asking that question, and you know, the inputs
may change, but the question won't change, and then whatever
whatever comes out the other side will be based on
our assessment of the answers to those questions. Always, we're
always going to be seeking to maximize the impact of
the funding that we provide towards accelerating exciting discoveries into
(22:13):
the clinic. And you did mention we have you know,
we're not tied to anyone cancer type of the Mark Foundation.
Speaker 2 (22:18):
So about half of our research projects cover.
Speaker 3 (22:22):
They typically some cover all cancer types because they're more
mechanistic and a little more fundamental in their nature. And
then some projects are would say multiple cancer types where
it's you know, it's something that it's still focused but
it's not necessarily focused on one very specific cancer. It's
focused on neuroendercrensumers, which cuts across a few different cancer
types or certain types of blood cancers, so leukemia's and
(22:45):
lymphoma's and my lomas right there are there are some
some areas so we we we range from focusing on
the very small, will even fund very rare cancer research
if we think that this funding will bring some bring
something through an inflection point, or we'll find research in
much more common cancer types. But there if we do,
(23:05):
the project that we're looking at needs to be something
that embodies some sort of risk in another way, you know,
whether it's bringing fields together like machine learning together with
cancer biology in a way that's new or doing something
that's not already being addressed elsewhere.
Speaker 1 (23:22):
I also wanted to get your before we move on
to more oncology focused conversation and your take on China.
The administration has its view on China, and it looks
like that they're making good progress on doing a possible
tariff or a trade deal, given some of the drum
beats that we hear about the rare els and the
(23:43):
access to chips, etc. But I've been going to the
region for the past twenty years and I have seen
a palpable change in the types of companies, going from
basically active ingredients for generics, to me too drug rugs,
to me better drugs, and now totally novel agents. It's
(24:05):
such that a lot of drugs that are coming out
of a region are being showing shown to be attractive
to US and European farmer companies. Now. One of the
things that I hear that that is really attractive about
the region is that they're much quicker to take a
concept to clinic and test it out, not by ignoring
(24:26):
ethics and patient safety, but just the amount of paperwork
is a lot less complicated. And then you've also got
the issue that there's a lot of variations on a
theme that are developed there, so you can kind of
pick from a menu almost. What is your perception how
(24:47):
much do you look at the region as a and
in general, Because at the end of the day, if
you're funding a grant where it's possible that it's going
to go into a phase one clinical trial, it sounds like,
assuming that people who want to fund it are able
to do that, they might be better to generate that
proof of concept trial in China or somewhere where the
(25:08):
speed with which you can recruit and do it and
calls is more attractive than in the US, although I
know there are efforts afoot to try and address them
in the US. To what's your perspective on.
Speaker 2 (25:19):
This, Yeah, to the last point.
Speaker 3 (25:21):
First, Yeah, I've heard the FDA's announced that they're going
to use AIM machine learning to try to make things.
Speaker 2 (25:29):
The process faster, and I hope that. I hope that
does work.
Speaker 3 (25:33):
I think for certain types of therapeutics, especially in the
cell engine therapy, their regulatory approach is more efficient and
expedient than ours is here now, especially on the GMP
side in terms of vector manufacturing and mixtures and things
like that that just lead to speed to clinic is
(25:55):
faster from a regulatory perspective. I think the other advantage
that they have right now, well, there's two others. One
you mentioned is cost cost or lower to run clinical
clinical development is the most expensive aspect of drug discovery.
The other the third is and this is also related
to cost, but it's it's it's time, the clinical operational effect.
You know, timelines are shorter there, they you know, site
(26:17):
efficiencies higher, they can enroll faster. Typically not all type
this is not this is more of a general statement.
I think for very specific cancer types. I don't know, uh,
you know, China may or may not be a place
where you'd see quicker enrollment, but in general you often
can see enrollment times in clinical trial site productivity be
higher in China. So so I think all those things
(26:39):
lead to reduce cost, more efficiency. I think it's still
a challenge for for drug developers outside of China to
look at you look and see how operations in China
running them at arm's length or trying to be there
on the ground, I think presents challenges. So I think
it's not a not an easy It's not an easy
(27:02):
answer for larger drug developers, I think in the smaller
biotech startup space there are The landscape is vast in
China and there are some amazing success stories in the
last few years. I mean legend was an example with
J and J going in and buying a China discovered
and developed drug for my loma a few years ago,
and that story.
Speaker 2 (27:22):
Will probably repeat.
Speaker 3 (27:23):
I spent a lot of time going to China, going back, yeah,
fifteen to twenty years when I was with Rosch and
later when I was with J and J, and so
I've seen on the scientific side, I mean, the culture
of science there is very strong. I've never seen, as
someone who spent the first half of my career as
an organic chemist working you know, working in connection with
(27:44):
the lab, I never saw so many organic chemists in
one place that as I saw when I would visit
Shanghai and Beijing and to go to different companies there.
So they have strength in terms of in terms of
their scientific capabilities.
Speaker 2 (27:59):
But I think, you know, it's not just China.
Speaker 3 (28:01):
You'll see Australia, for example, has a pretty forward looking
approach to regulatory in terms of cell therapy engine therapy.
So I think you're seeing people, you know, go in
Europe seems to be going in that direction as well too,
So I think the rest of the world is recognizing that,
you know, making clinical trial, clinical development more efficient, less
(28:23):
less costly is the way to go, and I think
you'll see that across the globe.
Speaker 1 (28:27):
Great, right, So let's go and talk about in the
last ten to fifteen minutes that we have together on
cology specifically, you're obviously at the cutting age, you have
your finger out. How many more different ways can I this?
Speaker 4 (28:39):
You have your finger on alls so and from outside
we of course see things when they kind of make
it to the clinic, and like the new modalities et
cetera that we're seeing, let's say, armored car ties, cartes
being designed through that method to be more act active
(29:00):
in solid tumors by specifics, clever cytokinds and you know,
and some of these, whether we believe it or not,
the data will continue to hopefully support that, some by
specifics that take two different mechanisms that are known but
seem to somehow bring some synergism some of the parts
(29:21):
is better than the individual. You know.
Speaker 1 (29:24):
We will find out this year whether VEGGIEFPD one by
specifics or tiget PD one by specific from our Zeneca
for example, genuinely make a difference to something that hadn't
worked so well as a as two single agents. But
so if you take all that, but if you look
at and put your crystal ball and look out five years,
(29:45):
what are the types of products ideas that we're going
to see that I should be at least teaching myself
the basic science on for when they come along.
Speaker 2 (29:57):
Well, I mean, I think more question.
Speaker 3 (30:00):
Yeah, yes, it's an exciting question though, I think, I mean,
I'll start with an area that I think you already
sound like you're pretty well up to speed on.
Speaker 2 (30:06):
But I think it's a it's an area that's still poised.
Speaker 3 (30:08):
It hasn't made a breakthrough yet despite all the efforts
for car TI for Solid tumor car TI for Solid Tumor,
has you know, we should be able to make this work.
Speaker 2 (30:19):
There's it's more.
Speaker 3 (30:20):
It's complicated, right, It's more complicated than the blood cancer setting.
The safety uh, you know considerations are certainly real, uh
and and we need to be careful with those. And
so armoring the cars up too much as a concern
not enough. They don't work. I think what the field
is poised for now is better understanding. This is gonna
this is being informed by real clinical data. What leads
(30:42):
to T cells the car te UH therapeutic modality itself
becoming more exhausted or starting off its life and a
place where it's going to be more prone to become exhausted.
So there's all kinds of concepts kind of baked into that,
going from the relationships with aging and cancer and so
in an age population where it's an atologous process and
so the immune cells have have you know, have an
(31:04):
aging component that we still need to understand more about,
and then we can if we understand what's making those
cells you know old, let's say, for lack of a
better word, we can we can help, you know, in
the x VVO process, rejuvenate them or in the or
put more energy into the alogenetic process, because we feel
like that's going to be the only thing that solves.
Speaker 2 (31:23):
The problem, you know.
Speaker 3 (31:24):
So we're working on answers for that, and I think
we'll see the car TI field for solid tumor hopefully
make some breakthroughs in the next you know, so by
five years from now, look at my crystal ball. I
think we'll have seen safe and efficacious cartes for solid
tumors and at least a couple of different indications, ideally
a pediatric and adult. One place I'm really excited to
(31:45):
see this progress is in glioblastoma, which is a disease
that's been you know, has not really had a therapeutic
breakthrough in over twenty years since timazolamide, more than twenty years.
So the car T cells showed some promise, but it's
not really durable, so we need to understand how to
keep those cells working for longer. But at least we
know there's some good targets in there now, which is encouraging.
(32:07):
And so you're going to see people working on those
targets and souping up their carte cells and trying to
get you know, deliveries and extra challenge getting things into
the brain that need to be there at the right levels,
et cetera, and the right combinations.
Speaker 2 (32:19):
Maybe even so so, but.
Speaker 3 (32:20):
I'm I'm uh, I'm excited about the next five years
in gliablastoma research. I think that field has been you know,
very long overdue for a breakthrough.
Speaker 2 (32:28):
I'd love to see what happen.
Speaker 3 (32:29):
It's such a you know, the the unmet need there
is so high. So that's so that's that's one area.
The other area you mentioned, you mentioned combinations. You mentioned
some really exciting by specific combinations, two different mechanisms on
one drug. That's you know, the famous you know, the
last year or so, the veg FPD one's got a
lot of attention digit PD one. Looking forward to seeing
how that plays out. I think understanding combination approaches better generally.
(32:54):
It's not a it's not a new concept that we
want to combine drugs, but I still think the cancer field.
As someone who worked in virology earlier in my career,
I feel like we were more successful and that was
maybe you could argue was technically easier, but HIV HTV.
We were able to bring these cocktails of combinations to
bear earlier in a way that prevented the prevented you know,
(33:18):
really worked for patients in a robust, durable way and
prevented the viruses from escaping. Let's say, right, so can
we do the same for cancer. I think the opportunity
for cancer to tie this back into something that's a
little more forward looking. I think we'll come in the
earlier treatment setting so we can get better early detection,
which is a diagnostic problem that we're still working on.
(33:39):
And then define a patient population in whom we can
practice disease interception now and treat patients earlier instead of
waiting till they're advanced or we detected later. In treating
metastatic disease, treat patients in an earlier setting, at earlier
stage or even pre cancer where we know the risk
is high enough to warrant treatment still, and use combination
(34:00):
to really just stop that, stop that cancer progression cold
in its tracks.
Speaker 2 (34:05):
Before it really ever gets started.
Speaker 3 (34:06):
So I think the next five years this kind of
intersection between early detection, disease interception, and therapeutic understanding of
how combinations and different agents can work together. Hopefully we'll
all converge to reduce cancer mortality. And I think the
early detection field is going to need that. So early
detection we can detect cancers earlier. But what do we
do about it? Does that really matter? Does ultimately does
(34:27):
that benefit patients? I think the only way you get
to a yes for that is if you can improve
your ability to intercept disease sooner or treat it sooner,
treat it earlier, and you'll need different drug combinations for that.
Speaker 1 (34:38):
Yeah. Yeah, you need to have one of your workshops,
need to be with insurance companies going forward, trying to
convince them that it's a good idea to prevent disease
then treat patients in the last life.
Speaker 2 (34:49):
Yeah.
Speaker 1 (34:50):
So one of the I'm going to do a little
lightning round type thing. I like the idea. Pretty much
every podcast has got one, you know, I thought we
might this, but before I get there is an example
that's just evolving right now, which is smoldering multiple my looma,
which is the it's not quite m gast. It's not
that very first spike in in monoclonal demopathies or anything
(35:15):
it is. But I mean, there are physicians who believe
it's a cancer, except it's not symptomatic yet. So and
we've just seen a trial read out for a single drug, Darzalex,
that's shown significant benefit in terms of prevention of it
to become symptomatic multiple my looma, And there, I think
(35:36):
is actually doable. We don't even need to do anything
new because you do the blood tests and you're there already,
so let's hope that other cancers can catch up with it.
You know, I'd love the idea of being able to
go in a big PET scan or CT scanner. Here
you go, you've got a two centimeter one centimeter thing
in your lung. It might not be cancer, or we're
(35:57):
just going to treat it for now, see what it happens.
Speaker 3 (35:59):
Right, So, okay, this is by way, that's exactly what
I'm talking about.
Speaker 2 (36:03):
Exactly.
Speaker 3 (36:03):
That's the disease interception, is exactly identifying those pre cancer
states that you could debate semantically whether or not you
even call them cancer, but still they're treatable and understanding
how to treat them.
Speaker 2 (36:15):
I'm very excited.
Speaker 1 (36:16):
Oh but you're I think our biggest challenge is going
to be with the payers and also the former companies,
because you're gonna end up with a much larger patient population.
They need to have to figure out whether how their
pricing structure works. So there's quite a lot of work
to be done there. Right, very quick, was we've got
about five five minutes, six minutes left and next big
jump in survival which tumor will that be? So let
(36:38):
me give you examples. We've had my Looma. We've had melanoma.
Breast cancer is pretty much you know, I mean, unfortunately,
there are still people who get caught too late for
the wrong reasons. But let's say it's relatively under control,
and we'll just keep what's the next one? Where is
your biggest where is your white hope? And I'm gonna
give you some leaders pank creative cleoma, kidney, Well.
Speaker 2 (37:00):
That's where the UNMETT need is the highest.
Speaker 3 (37:01):
In pancreas and glioma for sure, that's where the I
mean and ovarian I I would say the next big change, Well,
it's already here a little bit. So I'm gonna maybe
maybe maybe this answer is just sort of a I
hope it's not a cop out.
Speaker 2 (37:15):
But I think treating MSI high, if we're figuring out.
Speaker 3 (37:19):
A way that that I never saw a response, I mean,
the response rates that that we've seen in that trial
one hundred percent, right, they're amazing. So extending that to
all the cancers types to which that will apply at
at scale, because that hasn't really rolled out to the
proper population at large, I think people are MSI high
is always now a candidate for for checkpoint. But I
think you'll see that rolled out in a more intentional way.
You can see a lot of live stave. So it's
(37:40):
a cop out because it's not it's not one cancer type,
it's a it's a signature across multiple cancers.
Speaker 2 (37:44):
But you're going to see I'll take that.
Speaker 3 (37:46):
Yeah, So I think that's where you're gonna see in
the short term the biggest benefit to you know, uh,
to cancer patients in the short term. But okay, so
the longer term, I'm hopeful for gleablastoma and pancreas, but
I think those are still very hard and we've.
Speaker 1 (37:58):
Seen some really good cartida there. Yeah, I guess crossed
it would replicate. Now I'm going to end with AI
type questions hype versus real, you know, give the give us,
but we need to be quick here. Impact of AI
on biology and understanding basic biology hype or real hype? Okay,
(38:19):
Impact of AI on the basic steps of drug discovery,
designing molecules, designing clever antibodies, clever enzymes, et cetera. Hyper real, real,
impact on clinical trial design and klick trial conduct, real filing.
Speaker 3 (38:36):
Should be should be real real, I think that, But
certainly AI technology is ready to do that real and
whether it's actually happening or not yet, I'm not sure
it is, but but the technology AI technology is where
it should be to do.
Speaker 1 (38:47):
That, and then taking it to that stage that we've
kind of started with finding patients, finding them early, treating them.
Speaker 3 (38:54):
Early real I mean, I mean between hype and real,
go real.
Speaker 2 (38:58):
But there's a lot more work to be done to
implement that.
Speaker 3 (39:00):
I think machine learning has has brought early detection forward,
has really helped make early detection much better, but then
there's so many other challenges to make early detection translate
into better patient outcomes.
Speaker 1 (39:10):
Now, just as a matter of interest, I've just listened
to a podcast from knee Gium AI and they had
a conversation about this company that's just spun out of
Flagship VC that is trying to create an agentic AI
that comes up with hypothesis. I think that's what I
understood them say, comes up with the hypothesis, can actually
run the lab and test it and then refine his experiment.
(39:33):
That's what they're working on. So maybe biology will become
at least some form of reality at some point, But
I think.
Speaker 2 (39:40):
Yeah, type now, but it could become real. I definitely.
Speaker 3 (39:42):
I definitely wouldn't say I bulsh about the future for
biology for sure. For that I agree brilliantly.
Speaker 1 (39:48):
No, no, no, But that was interesting because I think
it's one of the first times I've heard it. I
know biontake through their one of their AI subsidiary that
they own, they have thought about talked about automated completely
in the box. Ultimately, Yeah, let's see.
Speaker 3 (40:03):
You could you could? You could imagine that for for sure.
I think I think the first thing AI should be
it has been applied and I think could be extended
to just inform experimental design better. Right understanding, we can
we can answer the questions with fewer experiments and using
AI to do that. Well, it is something that's that's real,
that's not hype, and that's that's here today. And I
think those principles will become as they feed into the
(40:26):
agentic approaches will then in the in the closed loop
you'll see that.
Speaker 2 (40:30):
But but we'll see.
Speaker 1 (40:30):
What Ryan, We've got a minute left. How would you
like to sign off?
Speaker 3 (40:34):
Well, I would just like to say, well, first of all, Sam,
I've enjoyed I've enjoyed speaking with you. Try this has
been a lot of fun. I would like to sign
off optimistically. I would like to say that I I
am truly inspired by how much how scientists and funding organizations, industry,
government really all do want to work together, uh in
(40:57):
ways to address the problems that face so many of
our friends and family that we've we've all been touched
by cancer someone we know. I mean, just it's such
a you know, it's such a prevalent condition. And as
the human population, you know, as longevity increases and aging increases,
I think cancer will continue to increase as much as
we're treating it.
Speaker 2 (41:18):
More effectively in some settings.
Speaker 3 (41:19):
So I'm very inspired by how how much the field
wants to come together and how much people enjoy working together.
So we're happy to you know, the Mark Foundation for
Cancer Research is happy to play our part in that
and to be a facilitator and a coalition builder bringing
scientists and like minded organizations together to uh to really
uh move uh move move science forward and bring deliver
(41:43):
new uh new drugs and new diagnostics for patients.
Speaker 1 (41:47):
That's brilliant. Thank you very much, Ryan Ranchelfed, CEO of
Mark the Mark Foundation, thank you for the good work
that you do. Is pretty clear that you that it
gives you a lot of energy doing this, so we
appreciate it, and I look forward to being invited to
some of your workshops and be a flyer all and maybe.
Speaker 2 (42:04):
Learn something absolutely absolutely.
Speaker 1 (42:07):
Thank you very much and speak to you soon. M
h m m
Host
Jonathan Palmer
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