September 15, 2025 • 58 mins
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On this week's episode, Lyle Small, Founder and CEO at Lahjavida, a dye drug conjugate start-up, talks about creating the famous color-changing technology that turned the mountains blue on cold Coors Light beer cans, to launching a dye-drug conjugate startup developing targeted cancer therapies. Small talks through Lahjavida's early preclinical work and the ongoing animal studies he hopes will secure an IND filing by 2027, his experience with scaling up manufacturing of new technologies, and his approach to leadership and company culture.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Ben Comer (00:07):
Welcome back to the Business of Biotech.
I'm your host, Ben Comer, ChiefEditor at Life Science Leader,
and today I'm excited to speakwith Lyle Small, founder and CEO
at Lahjavida, a companydeveloping dye- drug conjugates
to more precisely target cancerwith chemotherapy.
Lyle is a successful companyfounder.
(00:27):
His first company, ChromaticTechnologies Incorporated, or
CTI, made the Rocky Mountainsturn blue on the front of the
Coors Light can.
Once the beer inside got coldenough.
Americans over 35 years oldwill know exactly what I'm
talking about.
Lahjavida is Lyle's first foray, however, into the life
(00:47):
sciences sector and I'm excitedto learn about how the company
came together, what the overlapsare between commercial dye
manufacturing and drugdevelopment, the challenges that
he's encountered so far and hisplans to get to an IND filing
by 2027.
Thank you so much for beinghere, Lyle.
Lyle Small (01:07):
Thank you, good to be here, Ben.
Ben Comer (01:10):
I have to start with CTI and Coors Light, but maybe,
Lyle, you could talk a littlebit about your experience
founding that company your first, I believe, and where you got
the idea for making productstalk to customers.
Lyle Small (01:28):
Yeah, it's a little bit of an odd path.
I guess everybody has an oddpath.
I thought I was going to be anengineer at one point, trained
in bioengineering as anundergrad at Cornell and got
acquainted with thermochromicmaterials early on while I was
in college and followed thatpassion through my college years
(01:51):
and decided that, rather thanget a regular job, I would begin
a startup and see how far ittook me, I don't know.
I guess it's 32 years later.
Here we are.
I guess it's 32 years later,here we are.
So yeah, before graduation weincorporated the company.
My parents were pretty dismayedto hear that Lyle had chosen to
(02:17):
do a startup right out ofcollege, but it turned out okay.
Ben Comer (02:21):
Yeah, so you started up the company.
You've been very successful asyour first company.
When did it occur to you thatit might be cool or useful or
interesting for a product totell a customer when it got cold
?
Lyle Small (02:46):
have been around for a long time.
Far back as the mid-70s people,you know, folks in Japan
actually figured out how tomicroencapsulate these dyes to
get them to change color.
The problem was always that thesize of these microcapsules was
way too big and it never reallywas a viable option for the
kinds of printing that I thoughtwould be interesting.
(03:06):
So the idea that you could havesomething that could make a can
or a bottle talk to a customerwasn't a new one.
But we were the ones thatactually figured out the
technology that enabled it,which was make the stuff on the
inside of these microcapsules alot better and make the
(03:30):
microcapsules themselves morestable and the right particle
size.
Yeah, that sort of thing.
You know, if we could possiblydo this thing, wouldn't it be
great?
If you know watching Coors Lightcommercials, you know you were
probably familiar with the timewhen the commercials about the
(03:54):
cold terrain of Coors Lightracing through the Arctic.
You know they were all aboutcold because a warm Coors Light
isn't great.
All about cold because a warmCoors Light isn't great.
They wanted to own that space.
And watching these commercialsbecause I'm a big basketball fan
, all during the playoffs oneyear, I thought you know what?
(04:15):
We should figure this out.
We need to take another look athow we could reduce the
particle size enough to get ourstuff on a can, and that led to
six years of toil and failurebefore we figured it out In 2006
, I think was when they firstadopted it in the UK.
Ben Comer (04:38):
So how did it actually go down with cores?
I'm sorry, I'm very curiousabout this go down with Coors.
I'm sorry.
I'm very curious about this.
It's something that reallysticks out in my memory, kind of
along with hypercolor t-shirts,which I'm going to show my age
on that one.
They were popular in the 90sbut have mysteriously
disappeared.
But you're based in Colorado.
(04:59):
I mean, was it just kind of youknow, coors was, you know in
your backyard and was where youwanted to take it?
How did that evolve, like, howdid you actually get that
meeting and, you know,ultimately win that business?
Lyle Small (05:14):
So, like most entrepreneurs, I have a healthy
ego and I thought you know whywouldn't they talk to me.
Thought you know why wouldn'tthey talk to me.
I just get on the phone and say, hey, I've got something I
think could change your business, and was told to go away for
several years.
You know they're like thanks,son, but we've got it under
(05:35):
control.
But eventually they get tiredof hearing from you.
They realize you're not goingto go away.
It's a fairly common story,right?
You knock on the customer'sdoor enough and they finally let
you in.
The guy doing innovation forCoors was a really fantastic
gentleman that kind of put hisarm around me and said all right
(05:56):
, I'll humor you for a day orhere's an hour, give me your
pitch and I painted a prettygood picture.
Didn't have a product at thetime.
Of course you know, or likeimagine if you will uh, the
Coors Light can changing colorsand it was actually their
insight that they could tietheir core brand message of the
(06:21):
the mountains on the Coors Lightcan to color change.
You know, when the mountainsturn blue, it's as cold as the
Rockies.
That was not my idea.
That is all Coors Light and Igive them all the credit and you
talk about courage.
Right, you got this new startup.
These guys are teeny, littlecompany.
(06:42):
They're not far away so they'reconvenient, but they're a tiny,
tiny company.
We had sales under $3 million ayear at that point, primarily
doing checks, receipts andcoupons.
Color change that showed yourcheck was an original.
That was our primary technology.
That was our primary technology.
They took a big bet on us, ofcourse, did a lot of testing and
(07:12):
confirmation that it would workover the years, but it was a
mix of determination on our partand really impressive
innovative thinking on the partof the Coors Light brand team
that said you know what?
Let's see if this could happen.
If it could happen, I think itcould be impactful for our
business.
They talked the CEO into itonce they started seeing some
(07:35):
real stuff happen and his eyeslit up and said I think it's
brilliant, make it happen.
And that really pushed thingsinto the stratosphere.
You know we got the resourcesand the press time that allowed
us to perfect the technology.
Ben Comer (07:53):
I want to get to Lajavita in just a second, but I
have one more question aboutCTI.
I suspect that you know theCoors contract was a game
changer for the company.
When they finally said yes, youknow, you had to.
You had to scale up somewhatsignificantly.
I would imagine Can you can youtalk?
You know, first of all, youknow how did you convince them
(08:16):
that you could supply enough ofthe materials to to make this
work, and then how did you do itto make this work.
Lyle Small (08:29):
And then how did you do it Right so well?
There was no convincing CoorsLight.
We had to prove it right.
You know, like I could tellwhatever story I wanted Us.
Being able to ship thousands ofpounds of ink to go on aluminum
cans every month was somethingwe had to demonstrate, and had
to do that prior to them puttinga single can in the market.
(08:49):
So the scale up was complex,because the only way for us to
create microcapsules that wouldwork was for us to do the
microencapsulation, and we had avery specific process.
So scaling that from a littlebeaker to a giant tank was a
(09:10):
trick that took years right.
So we started in 2003 and thefirst cans in the UK were in
2006.
So there was this three yearperiod where we were trying to
really demonstrate that scalewas possible, and there are 30
(09:32):
plus manufacturing steps in this, because we micro encapsulate
and it's in a waterborneenvironment.
And then we have to teach thesecapsules to be happy in a
solvent-based environment of ametal decorating ink.
The capsules themselves have tobe very specific in terms of
(09:54):
their stability, because thatsolvent could destroy them and
that's usually the problem withthese systems.
So the complexity alone tookyears to work out and then
(10:21):
scaling each one'm sure thatyour listeners are familiar with
in the drug business.
But it taught me a lot oflessons about that process and
that you can't take anything forgranted.
You got to write everythingdown and teach people on the on
the manufacturing line how to doit.
These guys are the ones thatgot to execute and some of them
(10:44):
haven't gotten out of highschool right.
So you have to make itstraightforward.
It has to be repeatable.
You have to have a way toconfirm that it's right, because
you could have a tank full ofstuff that's worth $3,000 for a
single batch and if it's notright, you could turn that
(11:05):
$3,000 into $10,000 of waste bytaking it to the next step right
.
So you got a QC all along theway, and you know this is common
in manufacturing.
But I think that the unique partof what we had to do was the
size of our business and thedegree of complexity.
(11:26):
You know it's kind of likebuilding a transmission or
something you know.
Lots of steps along the way andwe failed dramatically at times
and had to throw a lot ofproduct away that didn't meet
our standards, and that isalways a tough choice for a
small company, but one thattaught me some crucial lessons.
(11:50):
The mountains have got to turnon, they've got to have the
right color, at the righttemperature in the right
environment every time, everyday, or we're cooked and it
would be a big black eye forCoors Light.
So that focused the mind.
You know I had a lot of verylong days for many years to get
(12:14):
it to work right, but it was.
Once you had it dialed in andwe got up and running.
It transformed us and actuallyallowed us not only to provide
basically free research andadditional innovations years
later with Coors Light, but itfunded the topic we're going to
(12:35):
cover today, which is La Llevida.
We would not have gotten intocancer research if we did not
have the revenue generated bythe Blue Mountains and Coors
Light.
Ben Comer (12:47):
And yeah, I said Americans over 35 will
definitely remember this, but itwasn't just Americans.
They were sending this productinto the UK and perhaps other
markets as well, all over Europe.
Lyle Small (12:58):
Yeah, we're in 30 countries.
Ben Comer (12:59):
Wow, okay, well, yeah , let's switch over to Lajavita.
What circumstances prompted youto, you know, pivot into life
sciences with this initial ideaof combining dyes with gold
nanoparticles for cancer?
Lyle Small (13:18):
So I've made clear we're in the dye business and I
was looking for a dye researcherand created some of the first
dyes for the what do you callthem?
The film, the photographic film, instant photography Sorry,
(14:02):
that's the word I'm looking for.
Yeah, yeah, so he did instantphotography.
Sorry, that's the word I'mlooking for.
Yeah, yeah, so he did instantphotography.
Then, of course, kodak blows upand he starts working in
invisible dyes for the FBI andfor other security applications,
where you print somethingthat's invisible and then you
take a special light or specialgoggles and you can identify it.
(14:25):
He also undertook an effortwith some folks at Georgia State
to develop a dye that boundselectively to cancer cells, and
they worked on this thing foryears, filed a patent in 2006.
And the point was to inject itinto a patient, travels
throughout the body and onlybinds to cancer cells, and then,
(14:47):
when you open up a patient toremove their tumor, the surgeon
can use special goggles with aspecial lamp, because the tumors
will glow green and then so thesurgeon will know where to cut,
and that's still a bigchallenge for surgeons is
figuring out where the edge ofthe tumor is when you're inside
(15:09):
a person.
Well, this was going to solvethat problem and they were
working with Harvard and did alot of work on this.
And he showed me this on aFriday.
I said fantastic,congratulations.
He showed me the picture of amouse with a glowing dot on its
rear flank, which was a tumor.
(15:29):
It's called a xenograft tumorfor a mouse in colon cancer had
this colon cancer tumor and itwas glowing bright red.
And he said this is going tochange cancer treatment because
doctors are going to know whereto cut, how far to cut.
And I said this is going tochange cancer treatment because
doctors are going to know whereto cut, how far to cut.
And I said man, that soundsawesome, looking forward to
(15:52):
seeing the miracles.
You work on the Coors Light canand other applications.
And then two days later, I waswatching a 60 Minutes program
about a guy named John KanziusK-A-N-Z-I-U-S.
You can find it on YouTube.
They did this program wherethis guy had the idea to inject
(16:15):
gold nanoparticles into tumorsand then put patients in front
of radio wave machines to heatup the gold, because radio waves
pass through us every dayharmlessly but when they come in
contact with metal particles,the particles vibrate and heat
up and you can kill tumors.
(16:35):
He was showing that you couldraise the temperature inside of
a hot dog, for instance.
You know he was putting thishot dog in this radio wave
machine that had goldnanoparticles in it and he said
you can practically cook the hotdog in one spot and leave the
rest of the hot dog temperatureunchanged.
And he said this would beperfect for tumors.
And he's right.
(16:56):
Hyperthermia in cancertreatment is well established
nowadays and it is excellent.
It's one of the best ways tokill tumors.
You get six degrees oftemperature increase and the
tumors, the cancer cells, die.
So we thought at the end of thisprogram they're talking about
(17:19):
the solution.
And they said so how would thiswork?
Would you just inject it?
And he said no, what we reallyneed is a targeting mechanism.
And it was kind of like thisshot out of the blue, you know,
like this is just too weird.
I just saw a targetingmechanism two days ago.
This dye could be attached tothese gold nanoparticles
(17:44):
potentially.
I mean I didn't know if it waspossible, I didn't know enough
about the dye or anything.
And so I went in the nextMonday and asked John about this
and he said well, in theory,absolutely.
So we filed a patent and Istarted working with Georgia
State to take their dyes andattach them to gold
nanoparticles, which are verycommon, and then, after two
(18:09):
years and more money than I wantto admit to having spent,
because my children are incollege now, we failed miserably
.
You know that money was justpoof gone and I gave up for two
years but turns out, I hiredanother Kodak chemist that kept
(18:31):
going.
We decided that we revived thisproject.
That's another long story.
It's one of those stories aboutyou know, like this thing just
ate at me.
You know we're moving ahead,growing the CTI part of the
business, but in the back of mymind I just could not let this
(18:53):
whole idea about a cancertreatment that would be brand
new to the world and transformcancer care Like it was this and
people nerds know what this isabout.
Right, if you're listening tome and you're in innovation,
then you get something underyour skin and it just gnaws at
your amygdala, right, it's justthis thing you dream about, you
(19:17):
think about it, and so I'm liketaking this as a sign.
I guess we should keep workingon this.
And I had a chemist that told methat he could make this tumor
targeting dye and it turns outhe could.
So that's when we started allover again, filed more patents
and actually got something thatwould work Hypothetically.
(19:39):
We got this tumor targeting dyeattached to gold nanoparticles
would attach itself actuallymore effectively than the pure
dye, to dozens of differenttypes of cancer.
And then we were putting thesecancer cells in radio wave
machines and cooking them andkilling them.
It was brilliant.
(20:00):
We had mice xenograft, micemodels that were taking up these
gold nanoparticles and thesedyes and were heating them,
shrinking tumors.
It's brilliant.
And then, you know, an engineeron our team said if you scale
this up, you're going to haveproblems because the device is
(20:21):
going be require so muchelectricity, it's going to cost
20 million bucks and you'regoing to need four of them in
every hospital.
It really is as an investabletechnology.
You got a problem.
That was 2019.
So this is a journey that takeshours to really describe, but
(20:45):
that's what led us to doing thesame thing with chemo drugs, and
that's where we are right now.
Ben Comer (20:52):
Now, when did you, at what point did you actually
found and launch Lajavita?
Lyle Small (20:58):
Lajavita was founded in 2018, after we started
shrinking tumors and, you know,actually heating up gold with
dye attached to it, selectivelybinding these to all kinds of
different cancer cells, andseeing these mice with glowing
xenograft tumors.
(21:18):
You know it was okay.
We've got to make thissomething new.
This was before we figured outthat you couldn't really invest
in it.
But 2018, we found La Llevidabecause we saw so much potential
.
Right, we had solved all thebig problems, except for the
device.
We had solved all the bigproblems except for the device.
A human-sized radio wavemachine was just going to be a
(21:41):
hill too big to climb for alittle company like ours.
Ben Comer (21:45):
Where did the name La Lla Vida come from?
I've been saying it wrong.
By the way, I think I said LaJavida last time.
Lyle Small (21:51):
That's all right.
Yeah, I have created a namethat no one can pronounce
Another problem with us nerdytypes.
So Laia, vida means the gift oflife in two different languages
.
I have a special place in myheart for Finland and Brazil,
and so this is the Laia meansgift in Finnish and vida means
(22:17):
life in Portuguese.
Ben Comer (22:19):
And you funded this company initially just from
proceeds at CTI.
Is that right?
Have you brought in additionalinvestors at this point, or what
are your plans, I guess, interms of funding right now?
Lyle Small (22:33):
Yeah, of funding right now.
Yeah, so CTI spends about.
We spend about 15% of ourrevenue on innovation, so we
have 35 unique technologies tothe world that no one else has.
We are an innovation-drivenorganization, so this was just
(22:56):
another research project.
Within CTI, we generally haveeight to 10 projects going at
once.
This was one that I was tryingto keep in the background for a
while.
You know, we're just going tolet Ray play around that's the
chemist's name Play around withthe dyes and the gold
nanoparticles in its free time.
(23:16):
We'll hire an engineer here andthere to see about heating up
the gold.
So this was funded.
We put in about three and ahalf million dollars of CTI's
own money before we spun it outActually, to date we're probably
about three and a half.
After we spun it out, it wasabout $2 million.
(23:40):
So total of three and a halfmillion dollars over the course
of that 10 or so years.
And eventually we spun out thatwe started this company but it
was still relying on CTI forfunding and doing all the basic
research.
But in 2023, we decided okay,we're going to spin this out,
(24:03):
transfer the technologycompletely.
It's going to stand on its own.
We're ready to go out into themarketplace and raise some seed
capital.
So we had some non-dilutivefunding from local foundations
here that love the idea oftargeted chemotherapy or
(24:23):
hyperthermia with goldnanoparticles.
They put money into us to thetune of about a million and a
half dollars on top of the moneythat we had put in, and now
we've raised another in thismost recent seed round that
we're trying.
We're now at the stage where wecan do pre-IND studies.
(24:45):
Our IND enabling work isbeginning now with Syngene, who
I'm sure your listeners haveheard of.
They are off and running theearly.
You know this is.
You heard it here first.
The last couple of weeks wehave they've been repeating the
work that we did in the priorthree years on cancer cells.
(25:08):
We showed very high efficacy onthree different cancer cell
lines in previous work.
That work was confirmed bySyngene.
So when you get a test resultyou feel like you've got
confidence in it.
You've repeated it severaltimes.
But when another company getsexactly the same results,
(25:31):
another research group getsexactly the same results in
Bangalore, india, it's hard toargue with those results.
And so we're getting equivalentefficacy to pure chemotherapy
drugs.
Nanomolar IC50 numbers, sohighly toxic to cancer cells,
very selective uptake and oncewe start doing the animal
(25:56):
studies we've already done fouranimal studies ourselves on lung
and colon cancers we're goingto start doing those animal
studies here in the fall andwe're going to file an IND in
2027.
We think we can get an approvalsometime in that year.
Ben Comer (26:15):
And you're, I guess the focus right now is on
linking the dye to chemo toestablish chemotherapy products
and improving their precision.
You're not still working ongold nanoparticles at this point
.
That's exactly right.
Lyle Small (26:29):
So we've set aside gold nanoparticles.
It's still being.
Actually there's some studiesbeing done by the local
university because we got anengineer there who's ecstatic
about hyperthermia, especiallyin prostate cancer.
He's found that you can doublethe heating with the same energy
when you attach these dyes togold nanomarticles.
I'm named in a biotech article,which is kind of funny, for
(26:57):
this particular approach.
It works well.
But he's focused on that, ourcompany.
We've discovered that we couldtake about 40% of the existing
chemotherapy drugs that haveever been developed and attach
them to this tumor-targeting dyeand make them safer and more
effective.
The dye uses a completelydifferent mechanism of action
(27:22):
compared to antibodies.
So antibody drug conjugates, aseveryone in biotech knows, are
the hottest thing right now.
There's a ton of these thingsin human trials there's 15 that
have been approved by the FDAand antibodies target specific
cancer cell types.
As I'm sure all of you thepeople that are listening know.
(27:43):
Antibodies identify specificepitopes on the surface of
cancer cells.
The antibody attaches to thoseon the surface and then this
cancer cell takes the wholething into itself and, once
inside, the cleavable linker,based on the chemistry of the
cancer cell, releases the chemodrug.
(28:04):
So antibody drug conjugateshave been around for a long time
, since the early 2000s, andeach one is worth over a billion
dollars.
Some of them are worth a couplebillion.
Each one is worth over abillion dollars, some of them
are worth a couple billion.
This most recent acquisition byPfizer of Cgen really
demonstrated the value ofantibody drug conjugates.
(28:25):
They have a tremendous.
They've done great things forpatients and we think that our
approach is like antibody drugconjugates, only better.
We think there's more potentialin this approach than antibody
drug conjugates.
That is an audacious statement.
I understand that I am part ofa company that we believe can
(28:51):
attach 40% of all chemotherapydrugs to a single dye that will
work on dozens of differentcancer types.
This dye has bound selectivelyto over 30 different types of
cancer.
Same dye because it uses adifferent mechanism of action.
That mechanism iswell-established, but it's
(29:14):
fascinating that this thing willwork on so many different types
of cancer.
But because it will, we've gotthe opportunity to kind of come
in and supplant antibody drugconjugates.
And why would I say that?
Well, antibodies have theirissues, as those who know the
(29:35):
business well, I didn't knowanything about antibody drug
conjugates until I got into this, but antibodies are hard to
make.
It turns out Really tough tomanufacture Once you make them.
They're not very stable.
They're huge molecules so theydon't cross the blood-brain
barrier.
They're problematic from a sideeffect standpoint.
(29:58):
Many of the most recent ADCsthat have been in human trials
have failed because of sideeffects.
They've either phase one orphase two.
They're failing and often it'sbecause of unpredictable immune
responses.
Antibodies cause immune issues.
(30:19):
They also have other issues.
There's actually an acquisitionmade recently.
I can't remember who bought thecompany, but all that company
does is identify the sideeffects of antibodies side
effects of antibodies.
That's because antibodies are aproblem.
(30:39):
Antibody drug conjugates havebeen and are fantastic.
However, they aren't the endgoal.
They have real problems thatour solution does not yet appear
to have right.
This dye is a simple moleculethat has shown zero toxicity.
(31:00):
We have demonstrated over andover again in fairly large
animal studies using small nudemice models, no impact of
toxicity from the dyesthemselves.
And actually we're not findingfree chemotherapy in the
(31:20):
bloodstream of these animals, sono free chemo drug is being
released systemically.
The dyes themselves do not showtoxicity.
We're getting 32% weight lossfrom pure doxorubicin, for
instance.
That's common.
Doxorubicin is called the reddevil because it's such a
(31:43):
horrible chemotherapy drug butit's got a $1.5 billion market
because doctors love it.
It shrinks tumors but it alsoreally messes up patients.
Tumors, but it also reallymesses up patients.
You get more than I think.
The number is 350 milligramsper kilogram of body weight of
doxorubicin Lifetime dose.
(32:03):
Your odds of permanentcardiotoxicity is over 40%.
You go over 400 milligrams andyou run the risk of giving your
patients a heart attack at therate of 60, 70% Really big
problems with doxorubicin.
(32:24):
When we attach doxorubicin toour dye, all those toxicities go
away.
We're getting an average weightloss of 4.5% from a cohort of
nine different mice, compared to32 percent weight loss with the
pure doxorubicin, and that's.
I mean that that alone is amassive step forward for cancer
(32:47):
care If we can eliminate or atleast significantly reduce these
kinds of side effects.
Now doctors don't have to worryabout that.
350 milligram per kilogramlifetime dose you can.
Dose reduction for doctors foroncology docs is one of their
(33:08):
biggest problems.
In order to save the life oftheir patient, they have to back
off on the medicine.
With our approach you don't.
You can continue to give thedose that's going to affect the
tumor for as long as you need to.
Ben Comer (33:26):
And because it's only affecting the tumor.
Lyle Small (33:29):
Exactly, yeah, it waits until it gets to the tumor
.
Once inside the tumor itcleaves Same cleavable linkers
that are used in antibody drugconjugates.
So the linker is not new.
The chemotherapy drugs, ofcourse, are not new.
The dye has been studied forsince 2006 and has never shown
(33:52):
any toxicity.
It is not FDA approved, but arelative of it is approved, and
we think that this thing has avery good shot at getting
approved by the FDA becausethere's there just no toxicity
signals your lead candidate.
Ben Comer (34:18):
You know, after you get through animal studies
you're not ready to decide onwhich chemotherapy agent you
know you might prioritize fordevelopment.
Lyle Small (34:23):
We've got.
So it's a great question.
We've got four DDCs that havebeen created and every one of
them worked.
Two different dyes and twodifferent payloads.
So Two different dyes and twodifferent payloads.
So SN38, which is the activeform of the prodrug, arenotecan,
and doxorubicin.
(34:44):
Attach both of those to our dyeto two different dye molecules,
and all four of these thingsbound selectively to cancer
cells, killed cancer cells at avery high rate, shrunk tumors in
mice in both lung and coloncancer.
So all of them were successful,but the doxorubicin with one
(35:06):
specific dye was the mostsuccessful.
So so far that's our lead.
Now we're repeating all thiswork with Syngene.
It's going to take a few months.
I don't like that.
I'd rather have it be done now,but a couple of months in the
grand scheme of things is notthat long a period.
(35:28):
Then we'll take it into our INDenabling work.
I think that we have a fifthcompound that stands a really
good chance of becoming our leadand that is a compound that
uses a brand new payload calledMMAE.
(35:49):
There are four different ADCs,antibody drug conjugates, that
use MMAE as a payload.
Mmae is 10 times more toxicthan doxorubicin, so this thing
cannot be used without severeprotection.
Right, you have to have itbound to an antibody or, in our
(36:14):
case, bound to our dye, so thatit travels systemically, it's
stable, but once it gets insidethe tumor, the MMAE is released
and it's proven to be a highlyeffective payload, as you can
imagine.
I mean, this thing is lightningin a bottle.
We're talking about picomolarIC50 numbers.
(36:37):
This thing is toxic, really,really hot.
So we're thinking maybe thisthing would take the lead in
some of our early studies.
But we'll find out.
Ben Comer (36:49):
Well, that's really interesting and exciting.
I wanted to ask you a questionabout animal studies and the IND
enabling work that you'regetting started on.
It's a topic that we don't talkabout that much on the podcast,
but every biotech builder isgoing to have to go through
(37:11):
those phases and so as someonewho is somewhat new you know
relatively speaking, I guess tothe life sciences sector Lyle,
you know give me a sense of youknow what it takes to do those
animal studies.
You've done some internally.
Now you're working with Syngeneto maybe repeat or expand that
(37:34):
work.
You'll go into your INDenabling studies.
Give me a sense of like youknow what was unexpected about
that, what some of thechallenges have been and maybe
like a kind of ballpark cost ofyou know what it will take to
get you through those INDenabling studies.
Lyle Small (37:50):
Yeah, so I'm cheap.
Ben Comer (38:17):
I do not like spending money and it has served
me well over the years.
However, once we got to a pointwhere we had seen enough of the
cell, information.
Lyle Small (38:20):
There's only so much .
You can do with two dimensionalmodelsdimensional models, and
those mice are pretty expensive.
I've heard, oh my goodness,shocking.
I think it's the, you know, theteeny little mouse is 300 bucks
, you know.
Uh, I, I believe that's what itcosts.
That's just for the mouse,that's not the house or feed or
any of that stuff.
These, these vivariums are justcrazy.
So you have to have, let's say,at least nine mice per cohort.
(38:41):
So this group has to be housedand fed in a very controlled
environment.
And then you got to grow thecancer cells in petri dishes for
a period of time until you getlarge enough to inject into the
mice.
And then you grow these tumors.
(39:02):
An individual, very basic mousestudy has run us on the order
of 80 to 100 thousand dollars.
So that's, you know, onecontrol and one test group.
If you want to do more than onetest group now, you know, just
(39:22):
add, add another $50,000 ontoeach one of those things.
They run real money, in otherwords, four or five weeks and,
um, that doesn't include thetime for the write-up.
We worked for a long time withthe Cancer Center drug
development folks at CU Anschutzhere in Colorado.
Really fantastic team ofprofessionals Was very pleased
(39:47):
with the work that they did withthe gold nanoparticles,
beginning in 2017.
In 2017.
They did some early stuff withthe chemotherapy conjugates in
2022.
Since then we've taken it outand working with a couple of
different CROs, but in all cases, in order for them to make any
(40:13):
money, they've got to chargesignificantly.
So we were in a luxurious spotwhere we had set aside, as I
said, 15% of our revenue goestoward R&D, and so we were able
to fund this to the tune ofseveral million dollars over the
course of several years overthe course of several years.
(40:40):
But at this stage, in order forus to have the kind of data
that is going to be persuasivefor the FDA, we got to raise
about, let's say, between fiveand eight million dollars.
We've raised a million and ahalf of that so far.
From you know local visionariesI'm actually one of them.
I will say I put in some of myown cash and so I'm coming in
(41:02):
with the same deal thateverybody else is, but we're
trying to raise money whereverwe can.
It is tough to get venturecapital interested at this stage
, as your listeners may befamiliar with Just in general.
It's hard to get venturecapital interested at this stage
, as your listeners may befamiliar with Just in general.
It's hard to get early venturemoney for oncology in particular
(41:24):
, however well, you add to thatthe overarching problems in the
biotech business problems in thebiotech business.
However, we think that this isa big enough idea that family
offices and interestedindividuals will find this
(41:45):
highly compelling.
You know the hope oftransforming chemotherapy and,
one day, possibly small moleculetargeted therapies that's, two
thirds of every cancer patientgets one or the other either
chemo or an SMTT.
That hope is just toocompelling for early stage
(42:09):
investors to pass up.
We're a small company but we'vegot a really impressive team
that's done this before.
Syngene has obviously done thishundreds of times and so, even
though we're coming out of theink business, we have a group of
people that can make it happen.
(42:31):
I don't have a PhD in molecularbiology.
I've got a bioengineeringdegree.
I know something about cellbiology and I'm learning more
about biotech every day.
It's, as you can imagine, quitean experience for a guy with
(42:51):
ink under his fingernails tocome into the biotech field.
But you hire good people thathave the right experience and
the path is fairly wellestablished.
That's one of the beauties ofthe FDA.
The downside is that the FDA isgoing to protect patients and
(43:12):
there's a very specific process.
It's incredibly expensive,incredibly time consuming, but
it's not a black box.
That's what I love about it andit either passes or it doesn't.
It either makes patients' livesbetter or it doesn't.
And if our solution doesn'tmake patients' lives better,
then the FDA should tell us togo away.
(43:33):
Make patients' lives betterthan the FDA should tell us to
go away.
So I'm not.
I don't necessarily have aproblem with the 80 to a hundred
million dollars we're going tohave to drop on pre-IND enabling
and then IND enabling and thenhuman trials between now and
2031.
But that it's a big hill toclimb and right now we got 1.5
(43:57):
million of the 90 million we'regoing to need.
If we can raise another 5 toget to human trials and that IND
is accepted by the FDA, that'sgoing to increase our valuation
and make raising the next 20 to25 million viable for phase one.
Phase one goes well and I amhighly confident that phase one
(44:23):
will go well because this thingis not toxic.
You know, we just see it overand over again these mice are
just fine after the end of thesestudies, and I think that you
know.
Of course humans are differentthan mice but based on the
conversations I've had withpeople, we have a lot of
(44:44):
confidence that phase one isgoing to go well and then phase
two is 30, I'm told, 30 plusOnce we get through that.
Now the company is a new entityand we're on a completely
different plane and I thinkventure capital will find us an
(45:08):
interesting target.
Ben Comer (45:11):
Are you considering I mean assuming an improvement in
the public markets?
I mean, have you thought aboutan IPO, like when that might
occur?
Lyle Small (45:19):
down the road Depends on the market.
You know phase two is going tobe 2029 and 2030.
So by that time I'm hoping thatthe blood in the streets will
(45:43):
subside a little bit you andeveryone else in the sector.
Yeah, right, yeah, that the IPOmarket will calm down a little
bit.
I'm open to IPOs if it makessense.
Being a public company issomething that makes me nervous.
I've got this pretty seriousindependence streak that I don't
(46:10):
like answering to people otherthan shareholders.
And if I've got 10 shareholders, fine.
If I've got a hundred thousandshareholders, uh, that now you
have a ring in your nose, asthey say.
You know you've got.
You got other people tellingyou, um, what you need to do
(46:31):
with your life day to day, andthat doesn't sound really great
to me.
But if it's required to changecancer treatment, I'll do it.
Ben Comer (46:38):
Yeah, yeah.
You mentioned the importance ofjust a few minutes ago of
hiring good people and I wonderwhat you might say about, you
know, the next hires that youwill need.
I don't know if you'll needlike a regulatory person to cope
what I was gonna say.
Lyle Small (46:54):
Yeah yeah, yeah, no regulatory is um such a key?
There's so few people I'vefound that uh that are out there
that want to join smallstartups with a keen
understanding of the innerworkings of the f.
As long as we can get the rightkind of help at this stage to
(47:18):
help us identify our lead andidentify our indication.
I've been listening long enoughto smart people talk about
these two topics to know thatthis isn't easy.
Choose well your lead compoundand, based on that lead compound
, there's interplay between thelead and the indication.
(47:38):
It isn't necessarily thebiggest market that you should
go after for your lead compound.
It is the market that you canassemble patients most readily
from right, yeah, right.
Where do you find thesepatients?
How much is each patient goingto cost you to attend to, to
(48:02):
take your compound?
How is this going to be runover time?
These are all big questionsthat are top of mind right now,
because we have to begin withthe end in mind, and this kind
of brings up another point thatI should make.
You know you're called thebusiness of biotech, even though
(48:23):
I'm not a biotech CEO.
It's business, and when I thinkabout how La Llebitia can be
successful, the question isalways what is the consumer need
that's being met by yourcompany?
Does your mission fill animportant need by customers?
(48:47):
And now, in this case, thecomplexity is ridiculous because
it's not just patients andpatients' families, but it's
doctors and insurance companies,it's the federal government,
it's big pharma should be one ofour customers at some level,
because this is a platformrecently, but we're just talking
(49:13):
about an augmentation forexisting chemotherapy that just
turns it off while it'scirculating in your body so that
it doesn't destroy your healthytissues and then lets it go
once it gets to the cancer cells.
So this, the thinking about howa business needs to run, are all
(49:34):
the same whether it'sbiotechnology or IT or software
or ink or selling pizzas.
Rate.
(49:56):
Building a team of people thatcan serve those needs
effectively and efficientlyevery day and make consumers
thrilled that you exist in theworld that is what business is
all about.
That's capitalism, and I thinkthat we're pretty clear.
It's never been more obvious,right, what the value
proposition is for a productthan what we're bringing to the
(50:18):
table here.
Ben Comer (50:22):
We talked a little bit about you know you shared
some of your experiences scalingup CTI.
Obviously, you're going to haveto do some.
You know, scale up as theassets progress at La Javita,
but you're also going to have toscale up your management team.
We've talked about, you know,hiring potentially a regulatory
person.
Maybe we can do a little bit ofrecruiting here.
(50:45):
Lyle, I'm curious about how youwould describe your management
style as a leader and maybe youknow how your colleagues and
staff would describe you.
Lyle Small (50:58):
This is a dicey question, so, but it's the only
question right For me personally, how I recognize the importance
of the role that I play.
And that is that.
That leads me to my firstcritical point.
With anybody that joins ourexecutive team, the most
(51:22):
important thing that anyonebrings to a team is the ability
to introspect Right.
This is this is true whetheryou're talking about a family,
you're talking about a footballteam, you're talking about a
team where you work or anorganization the ability for you
(51:43):
to look inward and say what ismy role here in this
organization, how do I make thisgroup better and where am I
falling short and can I take,accept feedback?
So when folks join our team,you know I've I'm a type A right
(52:07):
, I'm pretty intense, I get intoit, and some people, because I
talk like a football player, Iplayed a lot of football.
Some people, because I talklike a football player I played
a lot of football I amcompetitive, I am here to win,
(52:30):
and sometimes that intimidatespeople and I don't mean to be
intimidating, but I recognizethat I have to moderate that
because I am part of a group andhelping people feel comfortable
in that group, comfortable totell me the truth, as they see
it, is one of the most importantfunctions that I play.
I want to have a group ofpeople that are willing to tell
me what's on their mind, andthey're not going to do that if
(52:53):
they're nervous, right.
So they're also not going to doit if they think that the
people around them aren't goingto support them.
So, getting the best out ofpeople, especially when it comes
to the type of work that we'redoing at La Vida, we have to
(53:14):
have an environment where peopleare prepared to disagree and
have significant conflict, butnot personal conflict.
How do we have healthy conflictwhere the best ideas always win
, where no one takes thingspersonally if their idea isn't
(53:35):
the winner?
But getting good ideas on thetable of all kinds and then kind
of beating the hell out of them, you know like will your idea
survive?
The gauntlet of this teamthat's what I'm most proud of is
creating a group of individualsthat can be good friends and
(53:58):
also be able to say, no, I don'tlike that idea because of this,
this and this.
I think we should do this forthese reasons.
That's how companies ultimatelywin.
(54:24):
So when I interview folks for aleadership position, I am
searching for indications offour different personality
traits that I have found areincredibly valuable and
incredibly rare.
The first one is humility, as Ialluded to Right, and humility
is not some, you know idea ofself-loathing or you, you.
Humility is insecurity, somehow.
Humility is an accurateassessment of who you are and a
(54:44):
recognition that you shouldcontinually be reassessing who
you are, what you're good at andwhat you're not so great at.
And then curiosity, so, andthat kind of feeds this
introspection Curiosity aboutyourself first, but also
curiosity about what's in theheads of the people on the team.
(55:05):
Curiosity about what you, whatother people, are saying and why
they're saying it.
Curiosity about what motivatesothers customers, team members,
the marketplace.
And then the courage to acceptthe truth that you find as a
(55:27):
scientist, you're always lookingfor the truth, right, and you
sometimes don't like the truth.
The truth was that our goldnanoparticle idea was a shit
show waiting to happen.
You know it was going to be afailure, as much as I loved it.
(55:48):
I love the idea of hyperthermia.
It was my baby.
I had thought of that.
I watched the Kansia show.
I had to let it go.
Courage is required to say I waswrong.
Courage is required to say wehave to pivot.
Even though we love this idea,it's not going to work.
(56:09):
Courage to say I've beenfighting for the wrong thing
this past two months and I haveto apologize to this person, you
know, because maybe Imistreated them or whatever.
That takes courage.
It takes courage to do theright thing when it's
uncomfortable.
And then, finally, kindness, andthis one, you know, I always
(56:31):
like to think that I'm kind, butif I come across to someone as
overbearing, then kindnessrequires that I perfect, but
that you're striving each day tobe a little bit more courageous
, a little bit more humble, alittle bit more kind and a
(57:02):
little bit more curious.
I want you on my team Becauseyou got to be smart to have a
PhD, right.
You got to be smart to have tohave be a professional at the
highest level in biotech.
That's a given.
But smart people are also uheasy to find.
(57:22):
It's hard to find people thatare uh, going to let the the
truth always went out, whetherit's happens to be their idea or
not.
Ben Comer (57:33):
Well, um, that is an excellent place to end it, I
think.
Lyle, thank you so much forbeing on the show and telling us
about just sharing yourexperiences.
I really appreciate it.
Thank you, ben, it's been apleasure.
We've been speaking with LyleSmall, founder and CEO of La Lla
Vida.
I'm Ben Comer, and you've justlistened to the Business of
(57:55):
Biotech.
Find us and subscribe anywhereyou listen to podcasts, and be
sure to check out our new weeklyvideocasts of these
conversations every Monday underthe Business of Biotech tab at
lifescienceleadercom.
We'll see you next week andthanks, as always, for listening
.
Welcome back to the Business of Biotech.
I'm your host, Ben Comer, ChiefEditor at Life Science Leader,
and today I'm excited to speakwith Lyle Small, founder and CEO
at Lahjavida, a companydeveloping dye- drug conjugates
to more precisely target cancerwith chemotherapy.
Lyle is a successful companyfounder.
(00:27):
His first company, ChromaticTechnologies Incorporated, or
CTI, made the Rocky Mountainsturn blue on the front of the
Coors Light can.
Once the beer inside got coldenough.
Americans over 35 years oldwill know exactly what I'm
talking about.
Lahjavida is Lyle's first foray, however, into the life
(00:47):
sciences sector and I'm excitedto learn about how the company
came together, what the overlapsare between commercial dye
manufacturing and drugdevelopment, the challenges that
he's encountered so far and hisplans to get to an IND filing
by 2027.
Thank you so much for beinghere, Lyle.
Lyle Small (01:07):
Thank you, good to be here, Ben.
Ben Comer (01:10):
I have to start with CTI and Coors Light, but maybe,
Lyle, you could talk a littlebit about your experience
founding that company your first, I believe, and where you got
the idea for making productstalk to customers.
Lyle Small (01:28):
Yeah, it's a little bit of an odd path.
I guess everybody has an oddpath.
I thought I was going to be anengineer at one point, trained
in bioengineering as anundergrad at Cornell and got
acquainted with thermochromicmaterials early on while I was
in college and followed thatpassion through my college years
(01:51):
and decided that, rather thanget a regular job, I would begin
a startup and see how far ittook me, I don't know.
I guess it's 32 years later.
Here we are.
I guess it's 32 years later,here we are.
So yeah, before graduation weincorporated the company.
My parents were pretty dismayedto hear that Lyle had chosen to
(02:17):
do a startup right out ofcollege, but it turned out okay.
Ben Comer (02:21):
Yeah, so you started up the company.
You've been very successful asyour first company.
When did it occur to you thatit might be cool or useful or
interesting for a product totell a customer when it got cold
?
Lyle Small (02:46):
have been around for a long time.
Far back as the mid-70s people,you know, folks in Japan
actually figured out how tomicroencapsulate these dyes to
get them to change color.
The problem was always that thesize of these microcapsules was
way too big and it never reallywas a viable option for the
kinds of printing that I thoughtwould be interesting.
(03:06):
So the idea that you could havesomething that could make a can
or a bottle talk to a customerwasn't a new one.
But we were the ones thatactually figured out the
technology that enabled it,which was make the stuff on the
inside of these microcapsules alot better and make the
(03:30):
microcapsules themselves morestable and the right particle
size.
Yeah, that sort of thing.
You know, if we could possiblydo this thing, wouldn't it be
great?
If you know watching Coors Lightcommercials, you know you were
probably familiar with the timewhen the commercials about the
(03:54):
cold terrain of Coors Lightracing through the Arctic.
You know they were all aboutcold because a warm Coors Light
isn't great.
All about cold because a warmCoors Light isn't great.
They wanted to own that space.
And watching these commercialsbecause I'm a big basketball fan
, all during the playoffs oneyear, I thought you know what?
(04:15):
We should figure this out.
We need to take another look athow we could reduce the
particle size enough to get ourstuff on a can, and that led to
six years of toil and failurebefore we figured it out In 2006
, I think was when they firstadopted it in the UK.
Ben Comer (04:38):
So how did it actually go down with cores?
I'm sorry, I'm very curiousabout this go down with Coors.
I'm sorry.
I'm very curious about this.
It's something that reallysticks out in my memory, kind of
along with hypercolor t-shirts,which I'm going to show my age
on that one.
They were popular in the 90sbut have mysteriously
disappeared.
But you're based in Colorado.
(04:59):
I mean, was it just kind of youknow, coors was, you know in
your backyard and was where youwanted to take it?
How did that evolve, like, howdid you actually get that
meeting and, you know,ultimately win that business?
Lyle Small (05:14):
So, like most entrepreneurs, I have a healthy
ego and I thought you know whywouldn't they talk to me.
Thought you know why wouldn'tthey talk to me.
I just get on the phone and say, hey, I've got something I
think could change your business, and was told to go away for
several years.
You know they're like thanks,son, but we've got it under
(05:35):
control.
But eventually they get tiredof hearing from you.
They realize you're not goingto go away.
It's a fairly common story,right?
You knock on the customer'sdoor enough and they finally let
you in.
The guy doing innovation forCoors was a really fantastic
gentleman that kind of put hisarm around me and said all right
(05:56):
, I'll humor you for a day orhere's an hour, give me your
pitch and I painted a prettygood picture.
Didn't have a product at thetime.
Of course you know, or likeimagine if you will uh, the
Coors Light can changing colorsand it was actually their
insight that they could tietheir core brand message of the
(06:21):
the mountains on the Coors Lightcan to color change.
You know, when the mountainsturn blue, it's as cold as the
Rockies.
That was not my idea.
That is all Coors Light and Igive them all the credit and you
talk about courage.
Right, you got this new startup.
These guys are teeny, littlecompany.
(06:42):
They're not far away so they'reconvenient, but they're a tiny,
tiny company.
We had sales under $3 million ayear at that point, primarily
doing checks, receipts andcoupons.
Color change that showed yourcheck was an original.
That was our primary technology.
That was our primary technology.
They took a big bet on us, ofcourse, did a lot of testing and
(07:12):
confirmation that it would workover the years, but it was a
mix of determination on our partand really impressive
innovative thinking on the partof the Coors Light brand team
that said you know what?
Let's see if this could happen.
If it could happen, I think itcould be impactful for our
business.
They talked the CEO into itonce they started seeing some
(07:35):
real stuff happen and his eyeslit up and said I think it's
brilliant, make it happen.
And that really pushed thingsinto the stratosphere.
You know we got the resourcesand the press time that allowed
us to perfect the technology.
Ben Comer (07:53):
I want to get to Lajavita in just a second, but I
have one more question aboutCTI.
I suspect that you know theCoors contract was a game
changer for the company.
When they finally said yes, youknow, you had to.
You had to scale up somewhatsignificantly.
I would imagine Can you can youtalk?
You know, first of all, youknow how did you convince them
(08:16):
that you could supply enough ofthe materials to to make this
work, and then how did you do itto make this work.
Lyle Small (08:29):
And then how did you do it Right so well?
There was no convincing CoorsLight.
We had to prove it right.
You know, like I could tellwhatever story I wanted Us.
Being able to ship thousands ofpounds of ink to go on aluminum
cans every month was somethingwe had to demonstrate, and had
to do that prior to them puttinga single can in the market.
(08:49):
So the scale up was complex,because the only way for us to
create microcapsules that wouldwork was for us to do the
microencapsulation, and we had avery specific process.
So scaling that from a littlebeaker to a giant tank was a
(09:10):
trick that took years right.
So we started in 2003 and thefirst cans in the UK were in
2006.
So there was this three yearperiod where we were trying to
really demonstrate that scalewas possible, and there are 30
(09:32):
plus manufacturing steps in this, because we micro encapsulate
and it's in a waterborneenvironment.
And then we have to teach thesecapsules to be happy in a
solvent-based environment of ametal decorating ink.
The capsules themselves have tobe very specific in terms of
(09:54):
their stability, because thatsolvent could destroy them and
that's usually the problem withthese systems.
So the complexity alone tookyears to work out and then
(10:21):
scaling each one'm sure thatyour listeners are familiar with
in the drug business.
But it taught me a lot oflessons about that process and
that you can't take anything forgranted.
You got to write everythingdown and teach people on the on
the manufacturing line how to doit.
These guys are the ones thatgot to execute and some of them
(10:44):
haven't gotten out of highschool right.
So you have to make itstraightforward.
It has to be repeatable.
You have to have a way toconfirm that it's right, because
you could have a tank full ofstuff that's worth $3,000 for a
single batch and if it's notright, you could turn that
(11:05):
$3,000 into $10,000 of waste bytaking it to the next step right
.
So you got a QC all along theway, and you know this is common
in manufacturing.
But I think that the unique partof what we had to do was the
size of our business and thedegree of complexity.
(11:26):
You know it's kind of likebuilding a transmission or
something you know.
Lots of steps along the way andwe failed dramatically at times
and had to throw a lot ofproduct away that didn't meet
our standards, and that isalways a tough choice for a
small company, but one thattaught me some crucial lessons.
(11:50):
The mountains have got to turnon, they've got to have the
right color, at the righttemperature in the right
environment every time, everyday, or we're cooked and it
would be a big black eye forCoors Light.
So that focused the mind.
You know I had a lot of verylong days for many years to get
(12:14):
it to work right, but it was.
Once you had it dialed in andwe got up and running.
It transformed us and actuallyallowed us not only to provide
basically free research andadditional innovations years
later with Coors Light, but itfunded the topic we're going to
(12:35):
cover today, which is La Llevida.
We would not have gotten intocancer research if we did not
have the revenue generated bythe Blue Mountains and Coors
Light.
Ben Comer (12:47):
And yeah, I said Americans over 35 will
definitely remember this, but itwasn't just Americans.
They were sending this productinto the UK and perhaps other
markets as well, all over Europe.
Lyle Small (12:58):
Yeah, we're in 30 countries.
Ben Comer (12:59):
Wow, okay, well, yeah , let's switch over to Lajavita.
What circumstances prompted youto, you know, pivot into life
sciences with this initial ideaof combining dyes with gold
nanoparticles for cancer?
Lyle Small (13:18):
So I've made clear we're in the dye business and I
was looking for a dye researcherand created some of the first
dyes for the what do you callthem?
The film, the photographic film, instant photography Sorry,
(14:02):
that's the word I'm looking for.
Yeah, yeah, so he did instantphotography.
Sorry, that's the word I'mlooking for.
Yeah, yeah, so he did instantphotography.
Then, of course, kodak blows upand he starts working in
invisible dyes for the FBI andfor other security applications,
where you print somethingthat's invisible and then you
take a special light or specialgoggles and you can identify it.
(14:25):
He also undertook an effortwith some folks at Georgia State
to develop a dye that boundselectively to cancer cells, and
they worked on this thing foryears, filed a patent in 2006.
And the point was to inject itinto a patient, travels
throughout the body and onlybinds to cancer cells, and then,
(14:47):
when you open up a patient toremove their tumor, the surgeon
can use special goggles with aspecial lamp, because the tumors
will glow green and then so thesurgeon will know where to cut,
and that's still a bigchallenge for surgeons is
figuring out where the edge ofthe tumor is when you're inside
(15:09):
a person.
Well, this was going to solvethat problem and they were
working with Harvard and did alot of work on this.
And he showed me this on aFriday.
I said fantastic,congratulations.
He showed me the picture of amouse with a glowing dot on its
rear flank, which was a tumor.
(15:29):
It's called a xenograft tumorfor a mouse in colon cancer had
this colon cancer tumor and itwas glowing bright red.
And he said this is going tochange cancer treatment because
doctors are going to know whereto cut, how far to cut.
And I said this is going tochange cancer treatment because
doctors are going to know whereto cut, how far to cut.
And I said man, that soundsawesome, looking forward to
(15:52):
seeing the miracles.
You work on the Coors Light canand other applications.
And then two days later, I waswatching a 60 Minutes program
about a guy named John KanziusK-A-N-Z-I-U-S.
You can find it on YouTube.
They did this program wherethis guy had the idea to inject
(16:15):
gold nanoparticles into tumorsand then put patients in front
of radio wave machines to heatup the gold, because radio waves
pass through us every dayharmlessly but when they come in
contact with metal particles,the particles vibrate and heat
up and you can kill tumors.
(16:35):
He was showing that you couldraise the temperature inside of
a hot dog, for instance.
You know he was putting thishot dog in this radio wave
machine that had goldnanoparticles in it and he said
you can practically cook the hotdog in one spot and leave the
rest of the hot dog temperatureunchanged.
And he said this would beperfect for tumors.
And he's right.
(16:56):
Hyperthermia in cancertreatment is well established
nowadays and it is excellent.
It's one of the best ways tokill tumors.
You get six degrees oftemperature increase and the
tumors, the cancer cells, die.
So we thought at the end of thisprogram they're talking about
(17:19):
the solution.
And they said so how would thiswork?
Would you just inject it?
And he said no, what we reallyneed is a targeting mechanism.
And it was kind of like thisshot out of the blue, you know,
like this is just too weird.
I just saw a targetingmechanism two days ago.
This dye could be attached tothese gold nanoparticles
(17:44):
potentially.
I mean I didn't know if it waspossible, I didn't know enough
about the dye or anything.
And so I went in the nextMonday and asked John about this
and he said well, in theory,absolutely.
So we filed a patent and Istarted working with Georgia
State to take their dyes andattach them to gold
nanoparticles, which are verycommon, and then, after two
(18:09):
years and more money than I wantto admit to having spent,
because my children are incollege now, we failed miserably
.
You know that money was justpoof gone and I gave up for two
years but turns out, I hiredanother Kodak chemist that kept
(18:31):
going.
We decided that we revived thisproject.
That's another long story.
It's one of those stories aboutyou know, like this thing just
ate at me.
You know we're moving ahead,growing the CTI part of the
business, but in the back of mymind I just could not let this
(18:53):
whole idea about a cancertreatment that would be brand
new to the world and transformcancer care Like it was this and
people nerds know what this isabout.
Right, if you're listening tome and you're in innovation,
then you get something underyour skin and it just gnaws at
your amygdala, right, it's justthis thing you dream about, you
(19:17):
think about it, and so I'm liketaking this as a sign.
I guess we should keep workingon this.
And I had a chemist that told methat he could make this tumor
targeting dye and it turns outhe could.
So that's when we started allover again, filed more patents
and actually got something thatwould work Hypothetically.
(19:39):
We got this tumor targeting dyeattached to gold nanoparticles
would attach itself actuallymore effectively than the pure
dye, to dozens of differenttypes of cancer.
And then we were putting thesecancer cells in radio wave
machines and cooking them andkilling them.
It was brilliant.
(20:00):
We had mice xenograft, micemodels that were taking up these
gold nanoparticles and thesedyes and were heating them,
shrinking tumors.
It's brilliant.
And then, you know, an engineeron our team said if you scale
this up, you're going to haveproblems because the device is
(20:21):
going be require so muchelectricity, it's going to cost
20 million bucks and you'regoing to need four of them in
every hospital.
It really is as an investabletechnology.
You got a problem.
That was 2019.
So this is a journey that takeshours to really describe, but
(20:45):
that's what led us to doing thesame thing with chemo drugs, and
that's where we are right now.
Ben Comer (20:52):
Now, when did you, at what point did you actually
found and launch Lajavita?
Lyle Small (20:58):
Lajavita was founded in 2018, after we started
shrinking tumors and, you know,actually heating up gold with
dye attached to it, selectivelybinding these to all kinds of
different cancer cells, andseeing these mice with glowing
xenograft tumors.
(21:18):
You know it was okay.
We've got to make thissomething new.
This was before we figured outthat you couldn't really invest
in it.
But 2018, we found La Llevidabecause we saw so much potential
.
Right, we had solved all thebig problems, except for the
device.
We had solved all the bigproblems except for the device.
A human-sized radio wavemachine was just going to be a
(21:41):
hill too big to climb for alittle company like ours.
Ben Comer (21:45):
Where did the name La Lla Vida come from?
I've been saying it wrong.
By the way, I think I said LaJavida last time.
Lyle Small (21:51):
That's all right.
Yeah, I have created a namethat no one can pronounce
Another problem with us nerdytypes.
So Laia, vida means the gift oflife in two different languages
.
I have a special place in myheart for Finland and Brazil,
and so this is the Laia meansgift in Finnish and vida means
(22:17):
life in Portuguese.
Ben Comer (22:19):
And you funded this company initially just from
proceeds at CTI.
Is that right?
Have you brought in additionalinvestors at this point, or what
are your plans, I guess, interms of funding right now?
Lyle Small (22:33):
Yeah, of funding right now.
Yeah, so CTI spends about.
We spend about 15% of ourrevenue on innovation, so we
have 35 unique technologies tothe world that no one else has.
We are an innovation-drivenorganization, so this was just
(22:56):
another research project.
Within CTI, we generally haveeight to 10 projects going at
once.
This was one that I was tryingto keep in the background for a
while.
You know, we're just going tolet Ray play around that's the
chemist's name Play around withthe dyes and the gold
nanoparticles in its free time.
(23:16):
We'll hire an engineer here andthere to see about heating up
the gold.
So this was funded.
We put in about three and ahalf million dollars of CTI's
own money before we spun it outActually, to date we're probably
about three and a half.
After we spun it out, it wasabout $2 million.
(23:40):
So total of three and a halfmillion dollars over the course
of that 10 or so years.
And eventually we spun out thatwe started this company but it
was still relying on CTI forfunding and doing all the basic
research.
But in 2023, we decided okay,we're going to spin this out,
(24:03):
transfer the technologycompletely.
It's going to stand on its own.
We're ready to go out into themarketplace and raise some seed
capital.
So we had some non-dilutivefunding from local foundations
here that love the idea oftargeted chemotherapy or
(24:23):
hyperthermia with goldnanoparticles.
They put money into us to thetune of about a million and a
half dollars on top of the moneythat we had put in, and now
we've raised another in thismost recent seed round that
we're trying.
We're now at the stage where wecan do pre-IND studies.
(24:45):
Our IND enabling work isbeginning now with Syngene, who
I'm sure your listeners haveheard of.
They are off and running theearly.
You know this is.
You heard it here first.
The last couple of weeks wehave they've been repeating the
work that we did in the priorthree years on cancer cells.
(25:08):
We showed very high efficacy onthree different cancer cell
lines in previous work.
That work was confirmed bySyngene.
So when you get a test resultyou feel like you've got
confidence in it.
You've repeated it severaltimes.
But when another company getsexactly the same results,
(25:31):
another research group getsexactly the same results in
Bangalore, india, it's hard toargue with those results.
And so we're getting equivalentefficacy to pure chemotherapy
drugs.
Nanomolar IC50 numbers, sohighly toxic to cancer cells,
very selective uptake and oncewe start doing the animal
(25:56):
studies we've already done fouranimal studies ourselves on lung
and colon cancers we're goingto start doing those animal
studies here in the fall andwe're going to file an IND in
2027.
We think we can get an approvalsometime in that year.
Ben Comer (26:15):
And you're, I guess the focus right now is on
linking the dye to chemo toestablish chemotherapy products
and improving their precision.
You're not still working ongold nanoparticles at this point
.
That's exactly right.
Lyle Small (26:29):
So we've set aside gold nanoparticles.
It's still being.
Actually there's some studiesbeing done by the local
university because we got anengineer there who's ecstatic
about hyperthermia, especiallyin prostate cancer.
He's found that you can doublethe heating with the same energy
when you attach these dyes togold nanomarticles.
I'm named in a biotech article,which is kind of funny, for
(26:57):
this particular approach.
It works well.
But he's focused on that, ourcompany.
We've discovered that we couldtake about 40% of the existing
chemotherapy drugs that haveever been developed and attach
them to this tumor-targeting dyeand make them safer and more
effective.
The dye uses a completelydifferent mechanism of action
(27:22):
compared to antibodies.
So antibody drug conjugates, aseveryone in biotech knows, are
the hottest thing right now.
There's a ton of these thingsin human trials there's 15 that
have been approved by the FDAand antibodies target specific
cancer cell types.
As I'm sure all of you thepeople that are listening know.
(27:43):
Antibodies identify specificepitopes on the surface of
cancer cells.
The antibody attaches to thoseon the surface and then this
cancer cell takes the wholething into itself and, once
inside, the cleavable linker,based on the chemistry of the
cancer cell, releases the chemodrug.
(28:04):
So antibody drug conjugateshave been around for a long time
, since the early 2000s, andeach one is worth over a billion
dollars.
Some of them are worth a couplebillion.
Each one is worth over abillion dollars, some of them
are worth a couple billion.
This most recent acquisition byPfizer of Cgen really
demonstrated the value ofantibody drug conjugates.
(28:25):
They have a tremendous.
They've done great things forpatients and we think that our
approach is like antibody drugconjugates, only better.
We think there's more potentialin this approach than antibody
drug conjugates.
That is an audacious statement.
I understand that I am part ofa company that we believe can
(28:51):
attach 40% of all chemotherapydrugs to a single dye that will
work on dozens of differentcancer types.
This dye has bound selectivelyto over 30 different types of
cancer.
Same dye because it uses adifferent mechanism of action.
That mechanism iswell-established, but it's
(29:14):
fascinating that this thing willwork on so many different types
of cancer.
But because it will, we've gotthe opportunity to kind of come
in and supplant antibody drugconjugates.
And why would I say that?
Well, antibodies have theirissues, as those who know the
(29:35):
business well, I didn't knowanything about antibody drug
conjugates until I got into this, but antibodies are hard to
make.
It turns out Really tough tomanufacture Once you make them.
They're not very stable.
They're huge molecules so theydon't cross the blood-brain
barrier.
They're problematic from a sideeffect standpoint.
(29:58):
Many of the most recent ADCsthat have been in human trials
have failed because of sideeffects.
They've either phase one orphase two.
They're failing and often it'sbecause of unpredictable immune
responses.
Antibodies cause immune issues.
(30:19):
They also have other issues.
There's actually an acquisitionmade recently.
I can't remember who bought thecompany, but all that company
does is identify the sideeffects of antibodies side
effects of antibodies.
That's because antibodies are aproblem.
(30:39):
Antibody drug conjugates havebeen and are fantastic.
However, they aren't the endgoal.
They have real problems thatour solution does not yet appear
to have right.
This dye is a simple moleculethat has shown zero toxicity.
(31:00):
We have demonstrated over andover again in fairly large
animal studies using small nudemice models, no impact of
toxicity from the dyesthemselves.
And actually we're not findingfree chemotherapy in the
(31:20):
bloodstream of these animals, sono free chemo drug is being
released systemically.
The dyes themselves do not showtoxicity.
We're getting 32% weight lossfrom pure doxorubicin, for
instance.
That's common.
Doxorubicin is called the reddevil because it's such a
(31:43):
horrible chemotherapy drug butit's got a $1.5 billion market
because doctors love it.
It shrinks tumors but it alsoreally messes up patients.
Tumors, but it also reallymesses up patients.
You get more than I think.
The number is 350 milligramsper kilogram of body weight of
doxorubicin Lifetime dose.
(32:03):
Your odds of permanentcardiotoxicity is over 40%.
You go over 400 milligrams andyou run the risk of giving your
patients a heart attack at therate of 60, 70% Really big
problems with doxorubicin.
(32:24):
When we attach doxorubicin toour dye, all those toxicities go
away.
We're getting an average weightloss of 4.5% from a cohort of
nine different mice, compared to32 percent weight loss with the
pure doxorubicin, and that's.
I mean that that alone is amassive step forward for cancer
(32:47):
care If we can eliminate or atleast significantly reduce these
kinds of side effects.
Now doctors don't have to worryabout that.
350 milligram per kilogramlifetime dose you can.
Dose reduction for doctors foroncology docs is one of their
(33:08):
biggest problems.
In order to save the life oftheir patient, they have to back
off on the medicine.
With our approach you don't.
You can continue to give thedose that's going to affect the
tumor for as long as you need to.
Ben Comer (33:26):
And because it's only affecting the tumor.
Lyle Small (33:29):
Exactly, yeah, it waits until it gets to the tumor
.
Once inside the tumor itcleaves Same cleavable linkers
that are used in antibody drugconjugates.
So the linker is not new.
The chemotherapy drugs, ofcourse, are not new.
The dye has been studied forsince 2006 and has never shown
(33:52):
any toxicity.
It is not FDA approved, but arelative of it is approved, and
we think that this thing has avery good shot at getting
approved by the FDA becausethere's there just no toxicity
signals your lead candidate.
Ben Comer (34:18):
You know, after you get through animal studies
you're not ready to decide onwhich chemotherapy agent you
know you might prioritize fordevelopment.
Lyle Small (34:23):
We've got.
So it's a great question.
We've got four DDCs that havebeen created and every one of
them worked.
Two different dyes and twodifferent payloads.
So Two different dyes and twodifferent payloads.
So SN38, which is the activeform of the prodrug, arenotecan,
and doxorubicin.
(34:44):
Attach both of those to our dyeto two different dye molecules,
and all four of these thingsbound selectively to cancer
cells, killed cancer cells at avery high rate, shrunk tumors in
mice in both lung and coloncancer.
So all of them were successful,but the doxorubicin with one
(35:06):
specific dye was the mostsuccessful.
So so far that's our lead.
Now we're repeating all thiswork with Syngene.
It's going to take a few months.
I don't like that.
I'd rather have it be done now,but a couple of months in the
grand scheme of things is notthat long a period.
(35:28):
Then we'll take it into our INDenabling work.
I think that we have a fifthcompound that stands a really
good chance of becoming our leadand that is a compound that
uses a brand new payload calledMMAE.
(35:49):
There are four different ADCs,antibody drug conjugates, that
use MMAE as a payload.
Mmae is 10 times more toxicthan doxorubicin, so this thing
cannot be used without severeprotection.
Right, you have to have itbound to an antibody or, in our
(36:14):
case, bound to our dye, so thatit travels systemically, it's
stable, but once it gets insidethe tumor, the MMAE is released
and it's proven to be a highlyeffective payload, as you can
imagine.
I mean, this thing is lightningin a bottle.
We're talking about picomolarIC50 numbers.
(36:37):
This thing is toxic, really,really hot.
So we're thinking maybe thisthing would take the lead in
some of our early studies.
But we'll find out.
Ben Comer (36:49):
Well, that's really interesting and exciting.
I wanted to ask you a questionabout animal studies and the IND
enabling work that you'regetting started on.
It's a topic that we don't talkabout that much on the podcast,
but every biotech builder isgoing to have to go through
(37:11):
those phases and so as someonewho is somewhat new you know
relatively speaking, I guess tothe life sciences sector Lyle,
you know give me a sense of youknow what it takes to do those
animal studies.
You've done some internally.
Now you're working with Syngeneto maybe repeat or expand that
(37:34):
work.
You'll go into your INDenabling studies.
Give me a sense of like youknow what was unexpected about
that, what some of thechallenges have been and maybe
like a kind of ballpark cost ofyou know what it will take to
get you through those INDenabling studies.
Lyle Small (37:50):
Yeah, so I'm cheap.
Ben Comer (38:17):
I do not like spending money and it has served
me well over the years.
However, once we got to a pointwhere we had seen enough of the
cell, information.
Lyle Small (38:20):
There's only so much .
You can do with two dimensionalmodelsdimensional models, and
those mice are pretty expensive.
I've heard, oh my goodness,shocking.
I think it's the, you know, theteeny little mouse is 300 bucks
, you know.
Uh, I, I believe that's what itcosts.
That's just for the mouse,that's not the house or feed or
any of that stuff.
These, these vivariums are justcrazy.
So you have to have, let's say,at least nine mice per cohort.
(38:41):
So this group has to be housedand fed in a very controlled
environment.
And then you got to grow thecancer cells in petri dishes for
a period of time until you getlarge enough to inject into the
mice.
And then you grow these tumors.
(39:02):
An individual, very basic mousestudy has run us on the order
of 80 to 100 thousand dollars.
So that's, you know, onecontrol and one test group.
If you want to do more than onetest group now, you know, just
(39:22):
add, add another $50,000 ontoeach one of those things.
They run real money, in otherwords, four or five weeks and,
um, that doesn't include thetime for the write-up.
We worked for a long time withthe Cancer Center drug
development folks at CU Anschutzhere in Colorado.
Really fantastic team ofprofessionals Was very pleased
(39:47):
with the work that they did withthe gold nanoparticles,
beginning in 2017.
In 2017.
They did some early stuff withthe chemotherapy conjugates in
2022.
Since then we've taken it outand working with a couple of
different CROs, but in all cases, in order for them to make any
(40:13):
money, they've got to chargesignificantly.
So we were in a luxurious spotwhere we had set aside, as I
said, 15% of our revenue goestoward R&D, and so we were able
to fund this to the tune ofseveral million dollars over the
course of several years overthe course of several years.
(40:40):
But at this stage, in order forus to have the kind of data
that is going to be persuasivefor the FDA, we got to raise
about, let's say, between fiveand eight million dollars.
We've raised a million and ahalf of that so far.
From you know local visionariesI'm actually one of them.
I will say I put in some of myown cash and so I'm coming in
(41:02):
with the same deal thateverybody else is, but we're
trying to raise money whereverwe can.
It is tough to get venturecapital interested at this stage
, as your listeners may befamiliar with Just in general.
It's hard to get venturecapital interested at this stage
, as your listeners may befamiliar with Just in general.
It's hard to get early venturemoney for oncology in particular
(41:24):
, however well, you add to thatthe overarching problems in the
biotech business problems in thebiotech business.
However, we think that this isa big enough idea that family
offices and interestedindividuals will find this
(41:45):
highly compelling.
You know the hope oftransforming chemotherapy and,
one day, possibly small moleculetargeted therapies that's, two
thirds of every cancer patientgets one or the other either
chemo or an SMTT.
That hope is just toocompelling for early stage
(42:09):
investors to pass up.
We're a small company but we'vegot a really impressive team
that's done this before.
Syngene has obviously done thishundreds of times and so, even
though we're coming out of theink business, we have a group of
people that can make it happen.
(42:31):
I don't have a PhD in molecularbiology.
I've got a bioengineeringdegree.
I know something about cellbiology and I'm learning more
about biotech every day.
It's, as you can imagine, quitean experience for a guy with
(42:51):
ink under his fingernails tocome into the biotech field.
But you hire good people thathave the right experience and
the path is fairly wellestablished.
That's one of the beauties ofthe FDA.
The downside is that the FDA isgoing to protect patients and
(43:12):
there's a very specific process.
It's incredibly expensive,incredibly time consuming, but
it's not a black box.
That's what I love about it andit either passes or it doesn't.
It either makes patients' livesbetter or it doesn't.
And if our solution doesn'tmake patients' lives better,
then the FDA should tell us togo away.
(43:33):
Make patients' lives betterthan the FDA should tell us to
go away.
So I'm not.
I don't necessarily have aproblem with the 80 to a hundred
million dollars we're going tohave to drop on pre-IND enabling
and then IND enabling and thenhuman trials between now and
2031.
But that it's a big hill toclimb and right now we got 1.5
(43:57):
million of the 90 million we'regoing to need.
If we can raise another 5 toget to human trials and that IND
is accepted by the FDA, that'sgoing to increase our valuation
and make raising the next 20 to25 million viable for phase one.
Phase one goes well and I amhighly confident that phase one
(44:23):
will go well because this thingis not toxic.
You know, we just see it overand over again these mice are
just fine after the end of thesestudies, and I think that you
know.
Of course humans are differentthan mice but based on the
conversations I've had withpeople, we have a lot of
(44:44):
confidence that phase one isgoing to go well and then phase
two is 30, I'm told, 30 plusOnce we get through that.
Now the company is a new entityand we're on a completely
different plane and I thinkventure capital will find us an
(45:08):
interesting target.
Ben Comer (45:11):
Are you considering I mean assuming an improvement in
the public markets?
I mean, have you thought aboutan IPO, like when that might
occur?
Lyle Small (45:19):
down the road Depends on the market.
You know phase two is going tobe 2029 and 2030.
So by that time I'm hoping thatthe blood in the streets will
(45:43):
subside a little bit you andeveryone else in the sector.
Yeah, right, yeah, that the IPOmarket will calm down a little
bit.
I'm open to IPOs if it makessense.
Being a public company issomething that makes me nervous.
I've got this pretty seriousindependence streak that I don't
(46:10):
like answering to people otherthan shareholders.
And if I've got 10 shareholders, fine.
If I've got a hundred thousandshareholders, uh, that now you
have a ring in your nose, asthey say.
You know you've got.
You got other people tellingyou, um, what you need to do
(46:31):
with your life day to day, andthat doesn't sound really great
to me.
But if it's required to changecancer treatment, I'll do it.
Ben Comer (46:38):
Yeah, yeah.
You mentioned the importance ofjust a few minutes ago of
hiring good people and I wonderwhat you might say about, you
know, the next hires that youwill need.
I don't know if you'll needlike a regulatory person to cope
what I was gonna say.
Lyle Small (46:54):
Yeah yeah, yeah, no regulatory is um such a key?
There's so few people I'vefound that uh that are out there
that want to join smallstartups with a keen
understanding of the innerworkings of the f.
As long as we can get the rightkind of help at this stage to
(47:18):
help us identify our lead andidentify our indication.
I've been listening long enoughto smart people talk about
these two topics to know thatthis isn't easy.
Choose well your lead compoundand, based on that lead compound
, there's interplay between thelead and the indication.
(47:38):
It isn't necessarily thebiggest market that you should
go after for your lead compound.
It is the market that you canassemble patients most readily
from right, yeah, right.
Where do you find thesepatients?
How much is each patient goingto cost you to attend to, to
(48:02):
take your compound?
How is this going to be runover time?
These are all big questionsthat are top of mind right now,
because we have to begin withthe end in mind, and this kind
of brings up another point thatI should make.
You know you're called thebusiness of biotech, even though
(48:23):
I'm not a biotech CEO.
It's business, and when I thinkabout how La Llebitia can be
successful, the question isalways what is the consumer need
that's being met by yourcompany?
Does your mission fill animportant need by customers?
(48:47):
And now, in this case, thecomplexity is ridiculous because
it's not just patients andpatients' families, but it's
doctors and insurance companies,it's the federal government,
it's big pharma should be one ofour customers at some level,
because this is a platformrecently, but we're just talking
(49:13):
about an augmentation forexisting chemotherapy that just
turns it off while it'scirculating in your body so that
it doesn't destroy your healthytissues and then lets it go
once it gets to the cancer cells.
So this, the thinking about howa business needs to run, are all
(49:34):
the same whether it'sbiotechnology or IT or software
or ink or selling pizzas.
Rate.
(49:56):
Building a team of people thatcan serve those needs
effectively and efficientlyevery day and make consumers
thrilled that you exist in theworld that is what business is
all about.
That's capitalism, and I thinkthat we're pretty clear.
It's never been more obvious,right, what the value
proposition is for a productthan what we're bringing to the
(50:18):
table here.
Ben Comer (50:22):
We talked a little bit about you know you shared
some of your experiences scalingup CTI.
Obviously, you're going to haveto do some.
You know, scale up as theassets progress at La Javita,
but you're also going to have toscale up your management team.
We've talked about, you know,hiring potentially a regulatory
person.
Maybe we can do a little bit ofrecruiting here.
(50:45):
Lyle, I'm curious about how youwould describe your management
style as a leader and maybe youknow how your colleagues and
staff would describe you.
Lyle Small (50:58):
This is a dicey question, so, but it's the only
question right For me personally, how I recognize the importance
of the role that I play.
And that is that.
That leads me to my firstcritical point.
With anybody that joins ourexecutive team, the most
(51:22):
important thing that anyonebrings to a team is the ability
to introspect Right.
This is this is true whetheryou're talking about a family,
you're talking about a footballteam, you're talking about a
team where you work or anorganization the ability for you
(51:43):
to look inward and say what ismy role here in this
organization, how do I make thisgroup better and where am I
falling short and can I take,accept feedback?
So when folks join our team,you know I've I'm a type A right
(52:07):
, I'm pretty intense, I get intoit, and some people, because I
talk like a football player, Iplayed a lot of football.
Some people, because I talklike a football player I played
a lot of football I amcompetitive, I am here to win,
(52:30):
and sometimes that intimidatespeople and I don't mean to be
intimidating, but I recognizethat I have to moderate that
because I am part of a group andhelping people feel comfortable
in that group, comfortable totell me the truth, as they see
it, is one of the most importantfunctions that I play.
I want to have a group ofpeople that are willing to tell
me what's on their mind, andthey're not going to do that if
(52:53):
they're nervous, right.
So they're also not going to doit if they think that the
people around them aren't goingto support them.
So, getting the best out ofpeople, especially when it comes
to the type of work that we'redoing at La Vida, we have to
(53:14):
have an environment where peopleare prepared to disagree and
have significant conflict, butnot personal conflict.
How do we have healthy conflictwhere the best ideas always win
, where no one takes thingspersonally if their idea isn't
(53:35):
the winner?
But getting good ideas on thetable of all kinds and then kind
of beating the hell out of them, you know like will your idea
survive?
The gauntlet of this teamthat's what I'm most proud of is
creating a group of individualsthat can be good friends and
(53:58):
also be able to say, no, I don'tlike that idea because of this,
this and this.
I think we should do this forthese reasons.
That's how companies ultimatelywin.
(54:24):
So when I interview folks for aleadership position, I am
searching for indications offour different personality
traits that I have found areincredibly valuable and
incredibly rare.
The first one is humility, as Ialluded to Right, and humility
is not some, you know idea ofself-loathing or you, you.
Humility is insecurity, somehow.
Humility is an accurateassessment of who you are and a
(54:44):
recognition that you shouldcontinually be reassessing who
you are, what you're good at andwhat you're not so great at.
And then curiosity, so, andthat kind of feeds this
introspection Curiosity aboutyourself first, but also
curiosity about what's in theheads of the people on the team.
(55:05):
Curiosity about what you, whatother people, are saying and why
they're saying it.
Curiosity about what motivatesothers customers, team members,
the marketplace.
And then the courage to acceptthe truth that you find as a
(55:27):
scientist, you're always lookingfor the truth, right, and you
sometimes don't like the truth.
The truth was that our goldnanoparticle idea was a shit
show waiting to happen.
You know it was going to be afailure, as much as I loved it.
(55:48):
I love the idea of hyperthermia.
It was my baby.
I had thought of that.
I watched the Kansia show.
I had to let it go.
Courage is required to say I waswrong.
Courage is required to say wehave to pivot.
Even though we love this idea,it's not going to work.
(56:09):
Courage to say I've beenfighting for the wrong thing
this past two months and I haveto apologize to this person, you
know, because maybe Imistreated them or whatever.
That takes courage.
It takes courage to do theright thing when it's
uncomfortable.
And then, finally, kindness, andthis one, you know, I always
(56:31):
like to think that I'm kind, butif I come across to someone as
overbearing, then kindnessrequires that I perfect, but
that you're striving each day tobe a little bit more courageous
, a little bit more humble, alittle bit more kind and a
(57:02):
little bit more curious.
I want you on my team Becauseyou got to be smart to have a
PhD, right.
You got to be smart to have tohave be a professional at the
highest level in biotech.
That's a given.
But smart people are also uheasy to find.
(57:22):
It's hard to find people thatare uh, going to let the the
truth always went out, whetherit's happens to be their idea or
not.
Ben Comer (57:33):
Well, um, that is an excellent place to end it, I
think.
Lyle, thank you so much forbeing on the show and telling us
about just sharing yourexperiences.
I really appreciate it.
Thank you, ben, it's been apleasure.
We've been speaking with LyleSmall, founder and CEO of La Lla
Vida.
I'm Ben Comer, and you've justlistened to the Business of
(57:55):
Biotech.
Find us and subscribe anywhereyou listen to podcasts, and be
sure to check out our new weeklyvideocasts of these
conversations every Monday underthe Business of Biotech tab at
lifescienceleadercom.
We'll see you next week andthanks, as always, for listening
.
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