August 12, 2024 • 29 mins
In this episode we bring David Suhy, co-founder and Chief Scientific Officer at Earli back to the podcast. David shares the heartfelt founding story of Earli, the company's mission to make cancer a benign experience by catching it early, and their unique approach utilizing synthetic promoters for early cancer detection and treatment.
He discusses challenges faced in clinical trials, the importance of quality and safety in research, and provides advice for other startups in life sciences. David also talks about the recent advancements at Earli, their funding journey, and offers valuable insights on navigating the dynamic field of scientific innovation.
The episode concludes with a light-hearted discussion about David's passion for making pizzas in his backyard wood-fired oven.
00:00 Introduction and Podcast Overview
00:37 Guest Introduction: David Suhy from Earli
01:19 The Founding Story of Earli
04:24 Earli's Unique Approach to Cancer Detection
06:33 Challenges and Innovations in Cancer Treatment
10:06 Clinical Trials and Lessons Learned
15:30 Funding and Financial Strategies
18:56 Future Plans and Developments
21:14 Quality and Safety in Research
23:43 Advice for Entrepreneurs and Scientists
25:27 Fun Facts and Closing Remarks
https://www.earli.com
https://www.linkedin.com/in/davidsuhy/
Qualio website:
https://www.qualio.com/
Previous episodes:
https://www.qualio.com/from-lab-to-launch-podcast
Apply to be on the show:
https://forms.gle/uUH2YtCFxJHrVGeL8
Music by keldez
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:01):
Hi there! Welcome to the FromLab to Launch podcast by Qualio,
where we share inspiring storiesfrom the people on the front
lines of life sciences.
Tune in and leave inspired tobring your life saving products
to the world.
Meg Sinclair (00:17):
Thanks for joining us on from lab to launch today.
I'm Meg from Qualio and it's mypleasure to be your host and
introduce you to innovators inlife sciences.
If you haven't already, pleasesubscribe.
And we'd love it if you couldgive us a review on Apple or
Spotify.
And if you want to be on theshow, please see the application
linked in the show notes.
Today, we're talking to DavidSuhy, co founder and chief
(00:41):
scientific officer at Earli.
We actually had him on thepodcast almost two years ago, so
we're looking forward to hearingthe latest on his work in
oncology.
According to Earli's website, 40percent of us will develop
cancer in our lifetime and athird will die from it.
But what if we found and treatedthe cancer early enough so that
the majority of us could live?
(01:02):
That's early's mission to makecancer a benign experience by
catching and curing it early.
What an inspiring mission.
So let's bring David in and backon the show.
Welcome David.
David Suhy (01:14):
Thanks Meg.
It's a pleasure to be hereagain.
Nice to speak with you today.
Meg Sinclair (01:19):
For those of our listeners who are new to the
podcast and haven't heard thestory of early, could you tell
us a little bit about how itreally got started?
It's such a touching story.
David Suhy (01:28):
Yeah, absolutely.
Earliest company, it'sapproximately six years old now,
but really started first out ofa relationship between my co
founders, Cyriac Roeding and SamGambier.
Cyriac was a serial techentrepreneur who had just sold
his internet company.
(01:48):
For a fairly large sum of moneyand was looking for his next
thing in life and took a coupleof years off to explore what was
next.
Um, whether it would be in theInternet or the tech side of
things or something else.
And of all things, he got onThanksgiving Day.
(02:10):
a flyer in the mail that was alocal publication by Stanford
University talking about SamGambier's life as a professor at
Stanford University.
And more importantly, how he hadjust recently lost his son to
cancer.
Sam's son unfortunatelydeveloped cancer at age of 16
due to an inherited geneticdisorder.
(02:32):
And on Thanksgiving day, Syriacpicked up the article, read it.
wrote Sam a personal emailsaying he was touched by the
story, particularly on a daysuch as Thanksgiving and was
inspired by Sam's story andwould really like to meet him.
And Sam immediately responded.
If anyone of you out there knowsSam, that's Sam regardless if it
(02:53):
was his birthday orThanksgiving, um, but suggested
they meet together.
And talked about the inspiringstory behind Sam's own journey.
Not only as a training as anoncologist and clinician, but
how it impacted him personallythroughout cancer.
And they, they started talkingabout what was next in the field
(03:14):
of cancer and what was on thehorizon.
Um, and it was really thatrelationship that over the
course of the next.
Six months or so reallydeveloped into the early stages
of forming the company nowcalled early.
I was brought into the mix whenit was clear that, you know,
(03:36):
this was more than a an ideathat we really wanted to put a
company behind it.
Syria contacted me out of theblue through LinkedIn and we got
together for a coffee and overthe course of the next three to
four months really developed arelationship between the three
of us.
Talking about how we couldreally truly develop this as a
(03:59):
company, um, and take for thisnovel concept of terms of how to
manipulate the very genomebehind cancer and the genetic
changes that cancer imparts onthe cell to develop into a
business.
Um, and so the company was bornroughly then in June of 2018.
Meg Sinclair (04:21):
Thank you for that introduction for our new
listeners.
Can you explain to us a littlebit about how Earli is unique in
approaching early cancerdetection and compared to
traditional approaches?
David Suhy (04:33):
Yeah, we like to say that the company is not only
just in diagnostics, but alsotherapeutics.
And if you think abouttraditionally genomic medicines
or cancer treatments, thespecificity of delivering those
compounds to the tumors.
has greatly relied upon eitherthe composition of the lipid
(04:56):
nanoparticle.
For instance, things likedoxorubicin have been packaged
in lipid nanoparticles, but it'sthe lipid nanoparticles that
directs That docs to the tumoralternatively for viral vectors.
It's the protein inside of thecapsid.
Or is the capsid protein thatdirects that viral vector to the
(05:17):
cancer.
Now, gene therapy in the last 5to 10 years has now started to
realize that how you expressproteins becomes important.
And so, although in genetherapy, you might have tissue
specificity, there's been verylittle efforts towards trying to
tap into the geneticdysregulation, to hone your
(05:39):
promoter sequences, to only beselectively expressed within the
context of malignant tissues,and essentially remain
transcriptionally silent.
In either normal adjacenttissues comorbidities or other
types of comorbidities arebenign lesions as well.
So that the whole concept behindearly is how do we identify
(06:02):
those dysregulated pathways?
From the thousands of cancersamples that are out there, how
do we create something that hasbroad specificity in terms of
asking is a cancer or not, butalso works across different
genetic backgrounds in terms ofsensitivity?
And then how do we takeadvantage of that to create some
(06:25):
sort of molecular output toeither diagnose the disease or
to treat the cells themselves?
Meg Sinclair (06:33):
And so what are some potential challenges with
forcing cancer cells to reducethose synthetic biomarkers or
challenges that practitionersand patients have in adopting
this method?
David Suhy (06:42):
Yeah, I think it's a really great question.
Um, you know, to be clear, whatwe're essentially doing is, is
creating molecular lightswitches that only turn on in
the context of malignancy to anysubstantial degree.
If you have the ability todevelop these synthetic
promoters, then the world's youroyster in terms of payloads.
(07:03):
One of the ways we do this is weproduce proteins that are
expressed as epitopes on thecell surface that allow us to
use clinically validated orcommercially available radio
tracers to identify exactlywhich cancer cells have been
transfected and now have beenturned into a factory to produce
that epitope.
The same way you can exchangethe payload to express a
(07:26):
therapeutic protein to be ableto kill the cells.
Now, the trick of the system andwhat the biggest limitation is,
is that by using lipidnanoparticles, we're not talking
about achieving transfectionrates of 75, 80, 90%, or even
10%.
We typically see low singledigit percentage transfection of
(07:49):
cells.
which means that the number ofcells that actually express the
payload has some significantlimitations in terms of how the
output is going to be perceived.
For diagnostics, It's fairlystraightforward because
essentially you just need toproduce enough signal to noise
(08:10):
ratio to be able to see thesignal.
Now, I once had an investorchallenge me and say, David, I
don't understand how that'spossible.
You're going to transfect one or2 percent of cells.
How are you going to see thetumor?
And I explained it to him thisway.
I said, do you have a Christmastree?
He said, sure.
I said, do you put lights onevery single needle within the
(08:32):
Christmas tree?
He said, no, of course not.
We just put a string of lightsaround it.
And I said, what happens whenyou turn off the overhead
lights?
Do you know where in the roomthe Christmas tree is?
Do you know the size?
Do you know the shape?
And so for diagnostics, a lowtransfection efficiency, it's
not such a substantial barrier.
(08:52):
For therapeutics, it's a verydifferent story.
Can't produce a toxin that'sgoing to kill 1 percent or 2
percent of the cells.
Can't turn a radioligandDiagnostic into radio ligand
therapy, because even if you areusing an alpha or beta meter,
you're not going to kill enoughof the cells.
(09:13):
And you certainly won't expressenough to use something like an
ADC to be able to kill thecancer.
Instead, we take advantage orwe, we work within the
restrictions that is lowtransfection efficiencies.
And for our therapeutics, Wetend to focus on things that can
be expressed locally, directlyout of the tumors and into the
(09:36):
tumor microenvironment.
And as we know, and as we'velearned through all cancer over
the last 10 or 15 years, it'snot always about directly
killing the cell, but how do youstart to chain reaction?
How do you kick over the firstdomino of many dominoes to
essentially, um, have theability to effectuate?
(09:56):
Some sort of therapeuticoutcome, despite having limited
impact on the number of cancercells to treat.
Meg Sinclair (10:04):
Great.
Thank you for that explanation.
Last time we spoke, we hadtalked about a clinical trial
starting in Australia.
What lessons have you learned orhow has the platform moved on
from that clinical trial now?
David Suhy (10:17):
Yeah.
Thanks, Meg.
It's a great question.
When our initial clinicalproduct was using a cancer
activated motor to expresssecreted embryonic alkaline
phosphatase.
right?
A molecule that once producedfrom the cancer cell would be
shed into the bloodstream.
And the real question was, iswould it provide you an answer?
(10:39):
Do I have cancer?
Yes or no.
And but not much moreinformation beyond that.
And the promoter system that weused was a very bare basic
promoter that came out of Sam'slab at Stanford University.
What we quickly realized is, isthat with other competing
technologies, for instanceliquid biopsies or any of those
(11:02):
other early cancer detectionmodalities, that they were not
only getting an answer of wasthere cancer, yes or no, but in
many cases, things like themethylation pattern.
Um, Would tell you the tissue oforigin, although not
specifically where the cancerwas located.
So a couple of things we learnedfrom this clinical trial, we
(11:23):
we've discontinued the productjust to be clear, but the very
valuable learnings from theclinical study is, is that first
from a regulatory standpoint,it's very rare to use the
expression of a nucleic acid asa diagnostic product as a
therapeutic.
Sure.
Certainly as a biomarker, ofcourse.
(11:46):
But to have the direct productbeing produced as part of a
diagnostic, it's a bit atypical.
So going to agencies such as FDAand ultimately we ran the the
clinical study in Australia andunderstanding the regulatory
impact was very important.
Second, um, we understoodclinical utility and how
(12:08):
clinicians view the platform asa whole.
And I think it's very important.
Um, because At the end of theday, you don't want to work for
five, six years on a productthat clinicians ultimately don't
want.
And so getting that real timefeedback was ultra critical to
be able to shape the company'sstrategy moving forward and how
(12:31):
we're moving on to thisdiagnostic platform.
Because for us, what werecritical thing we learned from
the clinicians, yes or no wasnot a good enough answer for
them.
Their biggest challenges isoftentimes there's clinical
symptoms, but they don't know aspecific location of the
malignancy and by creating now alocalization product, that image
(12:55):
is exactly where the cancers aregoing to appear.
Gives a, a much more greaterclinical utility for the
clinicians.
Um, so I think in combinationalthough the product did not
move forward and many peoplewould consider that a failure,
we actually see it as a successbecause it, it informed us not
(13:16):
only the regulatory path, butexactly where the clinical
utility was going to be movingforward.
And it has thus shaped the, thecompany's path as we progress
into the future.
Meg Sinclair (13:28):
Great.
Sounds like a great use of timeand energy in that case.
Are there any other lessonslearned that you'd share with
other organizations going intotheir first phase of clinical
trials?
David Suhy (13:39):
Yes, absolutely.
First try not to start aclinical study when COVID's
going.
We happen to do this inAustralia and Australia.
Um, Behind China was probablythe second most locked down
country in the world in terms ofcities and populations.
And when we had clinicalendpoints, um, that required
(14:03):
patients to come in severaltimes after being dosed within
the first couple of weeks, superchallenging.
Second thing I would say,though, is, is that.
move quickly to get your firstproduct into the clinic.
Um, I think really quickly, youcan always be two years away
from your next clinical study.
(14:25):
And for young companies, thatcan be a killer.
Um, it is important to help younarrow your focus by defining
what the product is, what thetechnical challenges are, and
more importantly, understand thefeasibility of the entirety of
the process.
(14:45):
Um, and that's something youwant to define fairly early.
And not until you are six, sevenyears into a life cycle of a
company, and then figure outthat either from a technical
capability or some sort ofstrategic standpoint, it's
simply not going to work.
So my advice would be.
Always keep an eye towards theclinic.
(15:06):
Push, push, push to get into theclinic.
Of course, within the bounds ofmaking sure you have the
appropriate safety and as wellas efficacy, but push to get
into the clinic.
It's super important as a youngcompany to define those hurdles
and figure out ways around themto be able to move forward for
your future progress.
Meg Sinclair (15:28):
That's great advice.
Um, speaking of, you know,startups, your team has raised
significant funding from notableinvestors, and it can be
challenging for founders toraise capital in today's market.
How do you approach fundingtoday and how has your backing
supported your research andgrowth?
David Suhy (15:46):
Oh, wow.
Fabulous question.
Um, we've been very fortunate.
Um, you know, we were supportedin a very large seed series
round.
Um, A16Z was the primaryinvestor there.
COSLA came in in a series A andthen like many biotech
companies, we went to seek theelusive B round particularly in
(16:10):
the last year and a half.
Um, it's been called by manypublications, sort of the Valley
of Death Um, for many of thosecompanies out there trying to
raise capital.
It was difficult for us.
I'm not going to, um, make anysort of excuses.
I think, you know, we saw manyof our peer companies fall
(16:31):
apart.
I think the existing investors.
Have many portfolio companies introuble and it's asking going
back to the well is like askingthem to save their favorite
child.
Um, and so that becamechallenging for us as well.
So, you know, I think the keyfor us was being flexible and
adaptable.
(16:52):
And certainly while it's in nota founder's greatest joy to take
a sideways round or even aslight down round.
You do what's acceptable andneeded to be able to bring in
capital to keep the doors openand to be able to move forward.
And so ultimately that's what wewere resolved to do.
(17:13):
Instead of being able to find avery strong lead for a Series B,
When most new investors werejust trying to save their
existing companies.
Um, we were forced toessentially take a sideways
round.
We got buy in and pro rata from,from our investors.
Um, but just enough to be ableto raise smaller size chunks of
(17:37):
money to be able to keep thecompany.
Fiscally, um, in a, a goodposition and happy to report
that we've continued thatfundraising, um, have been able
to raise 92 million over theentirety of the company with,
with the last 32 coming in thelast few months.
So, um, it's been a.
(17:57):
A difficult process.
Um, my advice to founders isturn over rocks.
You wouldn't necessarily thinkto, um, we're all certainly
aware of the traditional venturecommunity, um, where we found a
little bit more traction as acompany is not only looking at
(18:17):
places like family offices, butalso international sources of
income.
Um, and I think, you know, um,you claw, you scratch, you
fight.
And you pull together the roundthat's going to be required to
keep the company moving forward.
And by doing so, then you putyourself in a position to
succeed and produce more resultsto be able to raise additional
(18:41):
monies on top of that.
I
Meg Sinclair (18:43):
think that's great advice to look in different
places besides just your usualplace for money to behind the
couch cushions is always a goodplace to look.
And that's no small
David Suhy (18:54):
change, but
Meg Sinclair (18:56):
metaphorically, um, what are your plans for the
next phase of development withall the funding you've got now?
David Suhy (19:04):
Yeah.
So we're, we're super excitedwhere, um, the company is
preparing to lock down its nextclinical product.
Um, around localization andessentially without getting too
deep into the weeds in terms ofthe science, this involves a
completely synthetic promoterthat we have shown has, um, not
(19:25):
only a great specificity, butgreat sensitivity across
different backgrounds of varioushuman primary tumors that are
derived from lung tissues.
Um, but on top of that.
What I'd say is, is that we'vemade such substantial progress
(19:46):
in terms of developing thesesynthetic promoters that it has
given us confidence that the offtissue specificity for things
like therapeutics, um, are, is,That much better.
And so more recently, we've nowstarted building out the
therapeutics arm of what thecompany is.
It's still based on the sameplatform of cancer activated
(20:08):
expression.
It's just simply swapping outthe payloads from an epitope
that it.
Again, it would be expressed ona cell surface for detection and
instead focusing on proteinsthat could be secreted locally
within the disease tissuesitself to broaden out the
therapeutic window and reallyhave an impact on the tumor and
(20:29):
tumor microenvironment as awhole.
So, the company has been rampingup very quickly.
We've been hiring like crazy andand um, And from a hiring
perspective, um, it has beensignificantly less challenging
because many of our sister andbrother companies are
struggling.
(20:50):
A lot of layoffs, but a lot ofgreat talent available to pull
into the company.
And so, for us, it's been alittle bit serendipitous and
we've really, um, are excitedabout the team that we're
building and more specificallyabout these programs we're
moving forward.
Meg Sinclair (21:07):
I'm excited for the team you're building and the
products you're building too.
We'll have to have you back inanother two years for another
update.
As a quality management softwareprovider, we have to ask about
Earli's approach to quality.
How does your team ensure thehighest standards of quality and
safety in research and clinicaltrials?
David Suhy (21:24):
Yeah.
You know, it's, it's such an,it's a really critical area that
if you're not paying attentionto it early and often, it's
going to come back and bite youin the behind later.
I would say, um, from early'sperspective, we always, and it
(21:45):
goes hand in hand with our, ourrationale of getting into the
clinic quickly.
Um, but you have to think aboutquality.
You have to think about safety.
You have to have systems inplace to understand what the
product is and what the processis.
There's an old saying in thefield, your process is your
(22:05):
product.
And the quality behind thatprocess and the quality behind
the product really defines howyou're going to go There's
nothing worse in this worldgetting to late stages of a
clinical submission for an indOr be halfway through a clinical
study and need to reproduceproduct And suddenly or have a
(22:26):
an sae or an ae occur Andsuddenly you realize there's
something that you overlooked orthere's a box that you haven't
checked or um You You know, itbecomes so blatantly obvious
after the fact.
And so really, um, again, myadvice to any of the younger
companies out there beyond this,right from the get go,
(22:49):
understand what the process isgoing to be, understand what the
product's going to be, havethose checks in place, set that
up early, because if you'redoing it last minute.
It's a recipe for disaster.
Um, and more often than not, youwill suffer, um, setbacks,
(23:09):
delays, or even worseconsequences if you don't pay
attention to your qualitysystems, the quality of your
product the planning, you know,an ounce of.
I don't know what the saying is.
I'm terrible with sayings, but Ithink it's a ulcer prevention is
worth a pound of cure orsomething like that.
And it's really the same, um,the same basic philosophy in
(23:34):
terms of setting yourself up forsuccess in the future.
Meg Sinclair (23:38):
That's great advice.
You've been imparting ourlisteners with lots of wisdom
today.
Since we last spoke in June of2022, do you have any other
lessons you've learned thatmight be useful to our
entrepreneurs or scientistslistening today?
David Suhy (23:52):
Yeah, I would I would say, you know, the
scientific field is a rapidlychanging, um, dynamic
environment.
Um, don't be afraid to takerisk.
Don't be afraid to stretch yourwings.
(24:13):
What we see today as the currentstate of art, even just two
years ago, from the last time wetalked has dramatically changed
AI was, was not much of a, Imean, it existed a few years
back, but it is inherentlypervasive in everything that we
do.
(24:33):
But understand that if you aregoing to be on the bleeding edge
there's risks, inherent risksbut really try to differentiate,
um, what you're trying to do.
Try to understand the clinicalutility.
Try to think ahead.
try to be two steps ahead ofwhere everyone else is.
(24:53):
And I think if you do that, notonly are you providing
potentially better outcomes forpatients, but also key
differentiators for yourself tobe in the field such that, you
know, when Funding does gettight or there's a dearth of
products that are Me Tooproducts that you will stand
(25:16):
head and shoulders aboveeverybody else.
And that more than anything elsehelps ensure your success moving
forward.
Meg Sinclair (25:24):
Great advice for our listeners.
And our last question is more ofa fun one.
I usually ask about books, but Isaw on your biography that you
are passionate about makingpizzas in your backyard.
Wood fired.
Oven.
So I thought I would ask, what'syour favorite pizza topping?
David Suhy (25:41):
Oh my gosh.
Oh, wow.
I could talk for another halfhour about this.
I I'm blessed that I have areally beautiful wood fired oven
in my backyard.
And, um, I live in NorthernCalifornia where artisan
ingredients are everywhere.
My favorite pizza at the momentis a rip off of Chris Bianco's
(26:04):
pizza.
He calls the Rosa.
And it's a combination of hardcheeses such as plavé vecchio
and a little bit of a meltycheese, like a fontina that goes
with pistachios.
rosemary, red onions, and thenan orange honey.
And I gotta tell you, it soundslike the most atypical pizza in
(26:25):
the world.
But I started making it about ayear ago.
And every time I have family orfriends over, it's the one that
they're always clamoring for.
You've got one pizza more tomake.
We have already eaten one.
We want another one of those.
So that, that would be my go topizza at the current moment.
Meg Sinclair (26:44):
Okay.
Well, I'll be looking up.
You and the next time I'm inNorthern California for that
pizza, that sounds delicious,David.
David Suhy (26:49):
Absolutely.
Meg Sinclair (26:51):
Well, thank you so much for joining us today and
updating us on Earli's progress.
Where can people go to learnmore, follow along and connect
with you?
David Suhy (26:59):
Yeah.
So, on LinkedIn, my name, D A VI D S U H Y is a great place to
connect with me directly.
If you're interested in learningmore about the company,
certainly the company website atearly.
com.
E A R L I.
Um, and it's a really happy toconnect with listeners and more
(27:21):
importantly, should take a lookat the website, get a little bit
more insight behind what we'redoing.
And if you're interested,certainly reach out to me
directly.
And we'll see where theconversation takes us from
there.
Meg Sinclair (27:33):
Great.
Thanks so much, David.
We'll post all that in the shownotes for our listeners.
Thank you so much for all yoursage advice today.
And we made me hungry for somepizza now.
David Suhy (27:43):
Thank you, Meg.
And, um, Who knows?
Let's see where we are two yearsfrom now.
It'd be great to check back inthen as well.
Meg Sinclair (27:50):
That would be great.
Thank you so much, David.
David Suhy (27:52):
Okay.
Take care.
Hi there! Welcome to the FromLab to Launch podcast by Qualio,
where we share inspiring storiesfrom the people on the front
lines of life sciences.
Tune in and leave inspired tobring your life saving products
to the world.
Meg Sinclair (00:17):
Thanks for joining us on from lab to launch today.
I'm Meg from Qualio and it's mypleasure to be your host and
introduce you to innovators inlife sciences.
If you haven't already, pleasesubscribe.
And we'd love it if you couldgive us a review on Apple or
Spotify.
And if you want to be on theshow, please see the application
linked in the show notes.
Today, we're talking to DavidSuhy, co founder and chief
(00:41):
scientific officer at Earli.
We actually had him on thepodcast almost two years ago, so
we're looking forward to hearingthe latest on his work in
oncology.
According to Earli's website, 40percent of us will develop
cancer in our lifetime and athird will die from it.
But what if we found and treatedthe cancer early enough so that
the majority of us could live?
(01:02):
That's early's mission to makecancer a benign experience by
catching and curing it early.
What an inspiring mission.
So let's bring David in and backon the show.
Welcome David.
David Suhy (01:14):
Thanks Meg.
It's a pleasure to be hereagain.
Nice to speak with you today.
Meg Sinclair (01:19):
For those of our listeners who are new to the
podcast and haven't heard thestory of early, could you tell
us a little bit about how itreally got started?
It's such a touching story.
David Suhy (01:28):
Yeah, absolutely.
Earliest company, it'sapproximately six years old now,
but really started first out ofa relationship between my co
founders, Cyriac Roeding and SamGambier.
Cyriac was a serial techentrepreneur who had just sold
his internet company.
(01:48):
For a fairly large sum of moneyand was looking for his next
thing in life and took a coupleof years off to explore what was
next.
Um, whether it would be in theInternet or the tech side of
things or something else.
And of all things, he got onThanksgiving Day.
(02:10):
a flyer in the mail that was alocal publication by Stanford
University talking about SamGambier's life as a professor at
Stanford University.
And more importantly, how he hadjust recently lost his son to
cancer.
Sam's son unfortunatelydeveloped cancer at age of 16
due to an inherited geneticdisorder.
(02:32):
And on Thanksgiving day, Syriacpicked up the article, read it.
wrote Sam a personal emailsaying he was touched by the
story, particularly on a daysuch as Thanksgiving and was
inspired by Sam's story andwould really like to meet him.
And Sam immediately responded.
If anyone of you out there knowsSam, that's Sam regardless if it
(02:53):
was his birthday orThanksgiving, um, but suggested
they meet together.
And talked about the inspiringstory behind Sam's own journey.
Not only as a training as anoncologist and clinician, but
how it impacted him personallythroughout cancer.
And they, they started talkingabout what was next in the field
(03:14):
of cancer and what was on thehorizon.
Um, and it was really thatrelationship that over the
course of the next.
Six months or so reallydeveloped into the early stages
of forming the company nowcalled early.
I was brought into the mix whenit was clear that, you know,
(03:36):
this was more than a an ideathat we really wanted to put a
company behind it.
Syria contacted me out of theblue through LinkedIn and we got
together for a coffee and overthe course of the next three to
four months really developed arelationship between the three
of us.
Talking about how we couldreally truly develop this as a
(03:59):
company, um, and take for thisnovel concept of terms of how to
manipulate the very genomebehind cancer and the genetic
changes that cancer imparts onthe cell to develop into a
business.
Um, and so the company was bornroughly then in June of 2018.
Meg Sinclair (04:21):
Thank you for that introduction for our new
listeners.
Can you explain to us a littlebit about how Earli is unique in
approaching early cancerdetection and compared to
traditional approaches?
David Suhy (04:33):
Yeah, we like to say that the company is not only
just in diagnostics, but alsotherapeutics.
And if you think abouttraditionally genomic medicines
or cancer treatments, thespecificity of delivering those
compounds to the tumors.
has greatly relied upon eitherthe composition of the lipid
(04:56):
nanoparticle.
For instance, things likedoxorubicin have been packaged
in lipid nanoparticles, but it'sthe lipid nanoparticles that
directs That docs to the tumoralternatively for viral vectors.
It's the protein inside of thecapsid.
Or is the capsid protein thatdirects that viral vector to the
(05:17):
cancer.
Now, gene therapy in the last 5to 10 years has now started to
realize that how you expressproteins becomes important.
And so, although in genetherapy, you might have tissue
specificity, there's been verylittle efforts towards trying to
tap into the geneticdysregulation, to hone your
(05:39):
promoter sequences, to only beselectively expressed within the
context of malignant tissues,and essentially remain
transcriptionally silent.
In either normal adjacenttissues comorbidities or other
types of comorbidities arebenign lesions as well.
So that the whole concept behindearly is how do we identify
(06:02):
those dysregulated pathways?
From the thousands of cancersamples that are out there, how
do we create something that hasbroad specificity in terms of
asking is a cancer or not, butalso works across different
genetic backgrounds in terms ofsensitivity?
And then how do we takeadvantage of that to create some
(06:25):
sort of molecular output toeither diagnose the disease or
to treat the cells themselves?
Meg Sinclair (06:33):
And so what are some potential challenges with
forcing cancer cells to reducethose synthetic biomarkers or
challenges that practitionersand patients have in adopting
this method?
David Suhy (06:42):
Yeah, I think it's a really great question.
Um, you know, to be clear, whatwe're essentially doing is, is
creating molecular lightswitches that only turn on in
the context of malignancy to anysubstantial degree.
If you have the ability todevelop these synthetic
promoters, then the world's youroyster in terms of payloads.
(07:03):
One of the ways we do this is weproduce proteins that are
expressed as epitopes on thecell surface that allow us to
use clinically validated orcommercially available radio
tracers to identify exactlywhich cancer cells have been
transfected and now have beenturned into a factory to produce
that epitope.
The same way you can exchangethe payload to express a
(07:26):
therapeutic protein to be ableto kill the cells.
Now, the trick of the system andwhat the biggest limitation is,
is that by using lipidnanoparticles, we're not talking
about achieving transfectionrates of 75, 80, 90%, or even
10%.
We typically see low singledigit percentage transfection of
(07:49):
cells.
which means that the number ofcells that actually express the
payload has some significantlimitations in terms of how the
output is going to be perceived.
For diagnostics, It's fairlystraightforward because
essentially you just need toproduce enough signal to noise
(08:10):
ratio to be able to see thesignal.
Now, I once had an investorchallenge me and say, David, I
don't understand how that'spossible.
You're going to transfect one or2 percent of cells.
How are you going to see thetumor?
And I explained it to him thisway.
I said, do you have a Christmastree?
He said, sure.
I said, do you put lights onevery single needle within the
(08:32):
Christmas tree?
He said, no, of course not.
We just put a string of lightsaround it.
And I said, what happens whenyou turn off the overhead
lights?
Do you know where in the roomthe Christmas tree is?
Do you know the size?
Do you know the shape?
And so for diagnostics, a lowtransfection efficiency, it's
not such a substantial barrier.
(08:52):
For therapeutics, it's a verydifferent story.
Can't produce a toxin that'sgoing to kill 1 percent or 2
percent of the cells.
Can't turn a radioligandDiagnostic into radio ligand
therapy, because even if you areusing an alpha or beta meter,
you're not going to kill enoughof the cells.
(09:13):
And you certainly won't expressenough to use something like an
ADC to be able to kill thecancer.
Instead, we take advantage orwe, we work within the
restrictions that is lowtransfection efficiencies.
And for our therapeutics, Wetend to focus on things that can
be expressed locally, directlyout of the tumors and into the
(09:36):
tumor microenvironment.
And as we know, and as we'velearned through all cancer over
the last 10 or 15 years, it'snot always about directly
killing the cell, but how do youstart to chain reaction?
How do you kick over the firstdomino of many dominoes to
essentially, um, have theability to effectuate?
(09:56):
Some sort of therapeuticoutcome, despite having limited
impact on the number of cancercells to treat.
Meg Sinclair (10:04):
Great.
Thank you for that explanation.
Last time we spoke, we hadtalked about a clinical trial
starting in Australia.
What lessons have you learned orhow has the platform moved on
from that clinical trial now?
David Suhy (10:17):
Yeah.
Thanks, Meg.
It's a great question.
When our initial clinicalproduct was using a cancer
activated motor to expresssecreted embryonic alkaline
phosphatase.
right?
A molecule that once producedfrom the cancer cell would be
shed into the bloodstream.
And the real question was, iswould it provide you an answer?
(10:39):
Do I have cancer?
Yes or no.
And but not much moreinformation beyond that.
And the promoter system that weused was a very bare basic
promoter that came out of Sam'slab at Stanford University.
What we quickly realized is, isthat with other competing
technologies, for instanceliquid biopsies or any of those
(11:02):
other early cancer detectionmodalities, that they were not
only getting an answer of wasthere cancer, yes or no, but in
many cases, things like themethylation pattern.
Um, Would tell you the tissue oforigin, although not
specifically where the cancerwas located.
So a couple of things we learnedfrom this clinical trial, we
(11:23):
we've discontinued the productjust to be clear, but the very
valuable learnings from theclinical study is, is that first
from a regulatory standpoint,it's very rare to use the
expression of a nucleic acid asa diagnostic product as a
therapeutic.
Sure.
Certainly as a biomarker, ofcourse.
(11:46):
But to have the direct productbeing produced as part of a
diagnostic, it's a bit atypical.
So going to agencies such as FDAand ultimately we ran the the
clinical study in Australia andunderstanding the regulatory
impact was very important.
Second, um, we understoodclinical utility and how
(12:08):
clinicians view the platform asa whole.
And I think it's very important.
Um, because At the end of theday, you don't want to work for
five, six years on a productthat clinicians ultimately don't
want.
And so getting that real timefeedback was ultra critical to
be able to shape the company'sstrategy moving forward and how
(12:31):
we're moving on to thisdiagnostic platform.
Because for us, what werecritical thing we learned from
the clinicians, yes or no wasnot a good enough answer for
them.
Their biggest challenges isoftentimes there's clinical
symptoms, but they don't know aspecific location of the
malignancy and by creating now alocalization product, that image
(12:55):
is exactly where the cancers aregoing to appear.
Gives a, a much more greaterclinical utility for the
clinicians.
Um, so I think in combinationalthough the product did not
move forward and many peoplewould consider that a failure,
we actually see it as a successbecause it, it informed us not
(13:16):
only the regulatory path, butexactly where the clinical
utility was going to be movingforward.
And it has thus shaped the, thecompany's path as we progress
into the future.
Meg Sinclair (13:28):
Great.
Sounds like a great use of timeand energy in that case.
Are there any other lessonslearned that you'd share with
other organizations going intotheir first phase of clinical
trials?
David Suhy (13:39):
Yes, absolutely.
First try not to start aclinical study when COVID's
going.
We happen to do this inAustralia and Australia.
Um, Behind China was probablythe second most locked down
country in the world in terms ofcities and populations.
And when we had clinicalendpoints, um, that required
(14:03):
patients to come in severaltimes after being dosed within
the first couple of weeks, superchallenging.
Second thing I would say,though, is, is that.
move quickly to get your firstproduct into the clinic.
Um, I think really quickly, youcan always be two years away
from your next clinical study.
(14:25):
And for young companies, thatcan be a killer.
Um, it is important to help younarrow your focus by defining
what the product is, what thetechnical challenges are, and
more importantly, understand thefeasibility of the entirety of
the process.
(14:45):
Um, and that's something youwant to define fairly early.
And not until you are six, sevenyears into a life cycle of a
company, and then figure outthat either from a technical
capability or some sort ofstrategic standpoint, it's
simply not going to work.
So my advice would be.
Always keep an eye towards theclinic.
(15:06):
Push, push, push to get into theclinic.
Of course, within the bounds ofmaking sure you have the
appropriate safety and as wellas efficacy, but push to get
into the clinic.
It's super important as a youngcompany to define those hurdles
and figure out ways around themto be able to move forward for
your future progress.
Meg Sinclair (15:28):
That's great advice.
Um, speaking of, you know,startups, your team has raised
significant funding from notableinvestors, and it can be
challenging for founders toraise capital in today's market.
How do you approach fundingtoday and how has your backing
supported your research andgrowth?
David Suhy (15:46):
Oh, wow.
Fabulous question.
Um, we've been very fortunate.
Um, you know, we were supportedin a very large seed series
round.
Um, A16Z was the primaryinvestor there.
COSLA came in in a series A andthen like many biotech
companies, we went to seek theelusive B round particularly in
(16:10):
the last year and a half.
Um, it's been called by manypublications, sort of the Valley
of Death Um, for many of thosecompanies out there trying to
raise capital.
It was difficult for us.
I'm not going to, um, make anysort of excuses.
I think, you know, we saw manyof our peer companies fall
(16:31):
apart.
I think the existing investors.
Have many portfolio companies introuble and it's asking going
back to the well is like askingthem to save their favorite
child.
Um, and so that becamechallenging for us as well.
So, you know, I think the keyfor us was being flexible and
adaptable.
(16:52):
And certainly while it's in nota founder's greatest joy to take
a sideways round or even aslight down round.
You do what's acceptable andneeded to be able to bring in
capital to keep the doors openand to be able to move forward.
And so ultimately that's what wewere resolved to do.
(17:13):
Instead of being able to find avery strong lead for a Series B,
When most new investors werejust trying to save their
existing companies.
Um, we were forced toessentially take a sideways
round.
We got buy in and pro rata from,from our investors.
Um, but just enough to be ableto raise smaller size chunks of
(17:37):
money to be able to keep thecompany.
Fiscally, um, in a, a goodposition and happy to report
that we've continued thatfundraising, um, have been able
to raise 92 million over theentirety of the company with,
with the last 32 coming in thelast few months.
So, um, it's been a.
(17:57):
A difficult process.
Um, my advice to founders isturn over rocks.
You wouldn't necessarily thinkto, um, we're all certainly
aware of the traditional venturecommunity, um, where we found a
little bit more traction as acompany is not only looking at
(18:17):
places like family offices, butalso international sources of
income.
Um, and I think, you know, um,you claw, you scratch, you
fight.
And you pull together the roundthat's going to be required to
keep the company moving forward.
And by doing so, then you putyourself in a position to
succeed and produce more resultsto be able to raise additional
(18:41):
monies on top of that.
I
Meg Sinclair (18:43):
think that's great advice to look in different
places besides just your usualplace for money to behind the
couch cushions is always a goodplace to look.
And that's no small
David Suhy (18:54):
change, but
Meg Sinclair (18:56):
metaphorically, um, what are your plans for the
next phase of development withall the funding you've got now?
David Suhy (19:04):
Yeah.
So we're, we're super excitedwhere, um, the company is
preparing to lock down its nextclinical product.
Um, around localization andessentially without getting too
deep into the weeds in terms ofthe science, this involves a
completely synthetic promoterthat we have shown has, um, not
(19:25):
only a great specificity, butgreat sensitivity across
different backgrounds of varioushuman primary tumors that are
derived from lung tissues.
Um, but on top of that.
What I'd say is, is that we'vemade such substantial progress
(19:46):
in terms of developing thesesynthetic promoters that it has
given us confidence that the offtissue specificity for things
like therapeutics, um, are, is,That much better.
And so more recently, we've nowstarted building out the
therapeutics arm of what thecompany is.
It's still based on the sameplatform of cancer activated
(20:08):
expression.
It's just simply swapping outthe payloads from an epitope
that it.
Again, it would be expressed ona cell surface for detection and
instead focusing on proteinsthat could be secreted locally
within the disease tissuesitself to broaden out the
therapeutic window and reallyhave an impact on the tumor and
(20:29):
tumor microenvironment as awhole.
So, the company has been rampingup very quickly.
We've been hiring like crazy andand um, And from a hiring
perspective, um, it has beensignificantly less challenging
because many of our sister andbrother companies are
struggling.
(20:50):
A lot of layoffs, but a lot ofgreat talent available to pull
into the company.
And so, for us, it's been alittle bit serendipitous and
we've really, um, are excitedabout the team that we're
building and more specificallyabout these programs we're
moving forward.
Meg Sinclair (21:07):
I'm excited for the team you're building and the
products you're building too.
We'll have to have you back inanother two years for another
update.
As a quality management softwareprovider, we have to ask about
Earli's approach to quality.
How does your team ensure thehighest standards of quality and
safety in research and clinicaltrials?
David Suhy (21:24):
Yeah.
You know, it's, it's such an,it's a really critical area that
if you're not paying attentionto it early and often, it's
going to come back and bite youin the behind later.
I would say, um, from early'sperspective, we always, and it
(21:45):
goes hand in hand with our, ourrationale of getting into the
clinic quickly.
Um, but you have to think aboutquality.
You have to think about safety.
You have to have systems inplace to understand what the
product is and what the processis.
There's an old saying in thefield, your process is your
(22:05):
product.
And the quality behind thatprocess and the quality behind
the product really defines howyou're going to go There's
nothing worse in this worldgetting to late stages of a
clinical submission for an indOr be halfway through a clinical
study and need to reproduceproduct And suddenly or have a
(22:26):
an sae or an ae occur Andsuddenly you realize there's
something that you overlooked orthere's a box that you haven't
checked or um You You know, itbecomes so blatantly obvious
after the fact.
And so really, um, again, myadvice to any of the younger
companies out there beyond this,right from the get go,
(22:49):
understand what the process isgoing to be, understand what the
product's going to be, havethose checks in place, set that
up early, because if you'redoing it last minute.
It's a recipe for disaster.
Um, and more often than not, youwill suffer, um, setbacks,
(23:09):
delays, or even worseconsequences if you don't pay
attention to your qualitysystems, the quality of your
product the planning, you know,an ounce of.
I don't know what the saying is.
I'm terrible with sayings, but Ithink it's a ulcer prevention is
worth a pound of cure orsomething like that.
And it's really the same, um,the same basic philosophy in
(23:34):
terms of setting yourself up forsuccess in the future.
Meg Sinclair (23:38):
That's great advice.
You've been imparting ourlisteners with lots of wisdom
today.
Since we last spoke in June of2022, do you have any other
lessons you've learned thatmight be useful to our
entrepreneurs or scientistslistening today?
David Suhy (23:52):
Yeah, I would I would say, you know, the
scientific field is a rapidlychanging, um, dynamic
environment.
Um, don't be afraid to takerisk.
Don't be afraid to stretch yourwings.
(24:13):
What we see today as the currentstate of art, even just two
years ago, from the last time wetalked has dramatically changed
AI was, was not much of a, Imean, it existed a few years
back, but it is inherentlypervasive in everything that we
do.
(24:33):
But understand that if you aregoing to be on the bleeding edge
there's risks, inherent risksbut really try to differentiate,
um, what you're trying to do.
Try to understand the clinicalutility.
Try to think ahead.
try to be two steps ahead ofwhere everyone else is.
(24:53):
And I think if you do that, notonly are you providing
potentially better outcomes forpatients, but also key
differentiators for yourself tobe in the field such that, you
know, when Funding does gettight or there's a dearth of
products that are Me Tooproducts that you will stand
(25:16):
head and shoulders aboveeverybody else.
And that more than anything elsehelps ensure your success moving
forward.
Meg Sinclair (25:24):
Great advice for our listeners.
And our last question is more ofa fun one.
I usually ask about books, but Isaw on your biography that you
are passionate about makingpizzas in your backyard.
Wood fired.
Oven.
So I thought I would ask, what'syour favorite pizza topping?
David Suhy (25:41):
Oh my gosh.
Oh, wow.
I could talk for another halfhour about this.
I I'm blessed that I have areally beautiful wood fired oven
in my backyard.
And, um, I live in NorthernCalifornia where artisan
ingredients are everywhere.
My favorite pizza at the momentis a rip off of Chris Bianco's
(26:04):
pizza.
He calls the Rosa.
And it's a combination of hardcheeses such as plavé vecchio
and a little bit of a meltycheese, like a fontina that goes
with pistachios.
rosemary, red onions, and thenan orange honey.
And I gotta tell you, it soundslike the most atypical pizza in
(26:25):
the world.
But I started making it about ayear ago.
And every time I have family orfriends over, it's the one that
they're always clamoring for.
You've got one pizza more tomake.
We have already eaten one.
We want another one of those.
So that, that would be my go topizza at the current moment.
Meg Sinclair (26:44):
Okay.
Well, I'll be looking up.
You and the next time I'm inNorthern California for that
pizza, that sounds delicious,David.
David Suhy (26:49):
Absolutely.
Meg Sinclair (26:51):
Well, thank you so much for joining us today and
updating us on Earli's progress.
Where can people go to learnmore, follow along and connect
with you?
David Suhy (26:59):
Yeah.
So, on LinkedIn, my name, D A VI D S U H Y is a great place to
connect with me directly.
If you're interested in learningmore about the company,
certainly the company website atearly.
com.
E A R L I.
Um, and it's a really happy toconnect with listeners and more
(27:21):
importantly, should take a lookat the website, get a little bit
more insight behind what we'redoing.
And if you're interested,certainly reach out to me
directly.
And we'll see where theconversation takes us from
there.
Meg Sinclair (27:33):
Great.
Thanks so much, David.
We'll post all that in the shownotes for our listeners.
Thank you so much for all yoursage advice today.
And we made me hungry for somepizza now.
David Suhy (27:43):
Thank you, Meg.
And, um, Who knows?
Let's see where we are two yearsfrom now.
It'd be great to check back inthen as well.
Meg Sinclair (27:50):
That would be great.
Thank you so much, David.
David Suhy (27:52):
Okay.
Take care.
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