January 15, 2021 • 32 mins
Dr. Ken Pienta, professor of Urology at Johns Hopkins University and acting CMO of Cue Biopharmaceuticals, talk about his experience in academic medicine and clinical trials. Dr. Pienta shares his thoughts on why physicians changing career focus isn't a negative but much for a positive. The discussion ends with a walk through of the process of clinical trial design and approval.
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Announcer (00:00):
Ask me MD medical school for the real world with
(00:03):
the MD Dr. DJ Verret
D.J. Verret, MD, FAC (00:06):
Greetings, and welcome to another edition
of Ask me MD medical school forthe real world. I'm Dr. DJ
Verret and today we're talkingwith Dr. Ken Pienta, professor
of oncology in urology at JohnsHopkins University and acting
chief medical officer of Qbiopharma about his experience
in academics and pharmaceuticalmedicine. We'll talk to Ken
(00:29):
right after this
Announcer (00:30):
Ask Me MD medical school for the real world.
D.J. Verret, MD, FAC (00:52):
Commerical Here Welcome back to ask me MD
(01:14):
medical school for the realworld. I'm Dr. D.J. Verret. And
today we have the great pleasureof talking with Dr. Ken Pienta,
professor of neurology andoncology at Johns Hopkins and
acting CMO of Cue Biopharma.
Ken, thanks for joining us.
Ken Pienta, MD (01:31):
I'm glad to be here. Thanks for inviting me.
D.J. Verret, MD, FACS (01:34):
So for all of our listeners out there
who may not know, can you giveus a little bit of history of
your background and kind of howyou got where you are today?
Ken Pienta, MD (01:43):
Sure, I trained in internal medicine at the
University of Chicago and thenwent on to do an oncology
fellowship at Johns Hopkins. Andafter that, I moved as an
assistant professor to WayneState, and then the University
of Michigan where I spent 20years running a translational
(02:03):
research lab, basically focusedon prostate cancer metastasis
and therapeutics, and at thesame time building up a practice
in advanced prostate cancer. Andthen after 20 years of doing
that, at the University ofMichigan, I moved to Johns
Hopkins, where I directedstarted to direct urology
(02:24):
research, as well as develop theprecision medicine program for
Johns Hopkins. And that bringsus here to today.
D.J. Verret, MD, FACS (02:35):
For for folks out there that may or may
not really understand could youkind of explain what precision
medicine is. I hear that term alot. But I don't know if
anyone's ever succinctlyexplained it to me.
Unknown (02:49):
Well, their their precision medicine is, you know,
to use the tried and truedefinition is treating the right
patient with the right drug atthe right time. And now in 2020
at the right place. And that'sespecially true now with COVID.
In that we have found that weneed to be much smarter about
(03:12):
how we treat people and where wetreat people do we really need
to bring them into the hospitalto treat them. So part of
precision is actually developingmethods to do video medicine
when it's appropriate andunderstanding when it's not
appropriate. That's all aboutprecision.
D.J. Verret, MD, FACS (03:32):
That's an interesting evolution. I hadn't
thought about the the rightplace. But but it continues, I
recently interviewed the CEO ofa mostly rural hospital system.
And he brought up the potentialfor virtual hospitals, that
they're starting to talk aboutkind of in line with what you're
you're talking about?
Unknown (03:51):
Yes.
D.J. Verret, MD, FACS (03:52):
What what kind of drew you to academic
medicine? Why did you why'd youwant to go in academics over
some other practice opportunity?
Unknown (04:01):
Well, for me, I loved the research. And I loved the
bench research part of it, thetranslation, and so to be
successful, and that what Iunderstood very early, was that
I was going to have to narrow myclinical focus that it was going
(04:22):
to if I was going to studyprostate cancer in the lab,
which is what I was trained todo. It made the most sense to
work with prostate cancerpatients, and therefore they
became my clinical laboratory.
And I would seamlessly do what Iwould look at what I was doing
in the lab and then apply thatto my patients in the clinic as
I tried to develop therapies andthen I would use their blood and
(04:45):
bone marrow and biospecimens andtissue to take back to the lab
to help me do better researchand then as I was developing
those resources programs, Irealized it was very difficult
to take any type of research,whether it be predictive
(05:07):
biomarkers or clinicaltherapeutics, all the way across
the finish line to an FDAapproved product that would help
actually help people across thatsort of gap. And so they started
working more and more withindustry to to understand and
(05:28):
translate what we were doing inthe lab, to patients, and then
from patients clinical trials,all the way to approval. And you
can't do that alone anymore,maybe 30 years, 4050 years ago,
you know, you've heard aboutpeople developing drugs at the
(05:48):
bench and then taking them allthe way to to, to the clinic and
beyond. It takes a village, ittakes a team it takes biotech
by, you know, pharma, academiclabs, etc, to do all that entire
translation across the spectrum.
And that's why I started alsoworking over the years with, you
(06:13):
know, biotech and pharma.
D.J. Verret, MD, FACS (06:17):
What do you find most rewarding about
your involvement in the wholedrug design and development
process?
Unknown (06:27):
You know, I find the bottom line is we're here to
help people and to try to make adifference and find ways that
decrease morbidity andmortality. And I find that each
step along the way, on any givenday is really exciting. And I
have the great privilege ofbeing able to do that dance of
(06:51):
of working in the lab, workingin the in the clinic, but then,
through my connections tobiotech, actually develop those
clinical trials into into largemulticenter trials to work
towards FDA approval. And I'vebeen able to do that now in my
(07:13):
life for not only drugs, butalso imaging agents as well as
bio biomarkers. Like forexample, I was the guy that
developed circulating tumorcells for prostate cancer as a
diagnostic marker.
D.J. Verret, MD, FACS (07:34):
When we were talking earlier, I use the
term non clinical medicine,which I think a lot of people
would say, when you're involvedin pharma, you're, you're in a
non clinical job. But But youbrought up a really good point
that, that no, it's not nonclinical. Can you kind of
explain your thoughts on that?
Unknown (07:52):
Yeah, I, you know, I use that we were talking offline
and you use that that term and Itook some umbrage.
D.J. Verret, MD, FACS (08:02):
That's true. I was I was kind of put in
a different way. But yes.
Unknown (08:07):
The reason why is because, you know, we need smart
people in every step of thisprocess of drug development,
and, and what I tell mystudents, my, my PhD students,
my clinical fellows, is thatit's where you find your joy,
but specifically, you know, forMDS, we need MDS who are trained
(08:33):
to take care of people whounderstand illness, who
recognize side effects, to workin industry, whether that's
biotech or pharma, as we developdrugs, so, for example, is to be
a medical director or a medicalmonitor, for a clinical trial of
(08:53):
a first inhuman drug requires,you know, that you have
expertise, that you canrecognize what side effects are,
and that you can recognize whenyour first inhuman drug might be
having an adverse side effect oradverse event. And that's it. So
(09:14):
you're you're taking care ofpeople, and you're watching the
drug develop. And you're and youAlthough you're not laying your
hands on them, you are directlyinvolved in their care, you are
making lifetime decisions aboutwhether they should continue on
a drug. You know, the recenthalt of the of the Merck study
(09:38):
with COVID is because there wasan MD in pharma. Not seeing
patients but recognizing thatthere was a weird side effect.
That that is that is clinicalmedicine to me. And I think
folks who are switching over toindustry potentially from
(09:58):
academics or from privatePractice to industry, because
they they just don't want to dofor example, the day to day
clinical patient caridy anymore.
They can, that's a veryrewarding track to to be able to
take care of people that way.
D.J. Verret, MD, FACS (10:19):
With your experience kind of being on the
clinical side, the academicside, and then the pharma side
now as an acting cmo with a witha biotech company in clinical
trials, what advice would yougive to physicians that may be
looking to transition into someof these pharmaceutical jobs?
Unknown (10:38):
Yeah, my, my, I guess my number one piece of advice is
to really clearly determine foryourself, what what you're
interested in doing what you'reexcited to do every day. And
they're the spectrum of, forexample, biotech. That means
(11:01):
that, you know, are you moreinterested in immunology? Are
you more interested inRheumatology? Are you more, you
know, find fight, you can findthere's so many companies out
there. And so manyopportunities, you can really
find the type of position thatyou want to with the kind of
drug you want to if you want tojust dabble, you know, to say,
(11:24):
is this interesting to me, thatmany of these companies have
advisory boards that you canbecome involved in as they try
to develop agents and they'relooking for a, for example, how
will this drug be used in theclinical practice you were in?
Whether and it doesn't matterwhether that was academics, or
(11:45):
private practice or largegroups, there's a lot of
opportunity there. The otherthing you have to think about
is, do you want to be inbiotech, which tends to be a
small, you know, smallerorganizations where you're going
to be the MD, and they're goingto be looking at you for your
for clinical acumen. Andunderstanding how a drug affects
(12:09):
patients. Where or do you wantto be part of a larger
organization, like a pharma, abig drug company, where you
might be asked to, you know,develop a particular agent
across multiple countries or doit, you know, we already know
the toxicities and what theyneed somebody to run a phase
three, study. The, the also, theother thing you can do is, you
(12:35):
know, depending on yourtraining, you can get involved
in, quite frankly, on the nonclinical side, do you want to
develop help develop FDApackages, you know, the the ind
investigational new drugpackages. And to do that, again,
you can there, there are ways todo that, where you can sort of
(12:57):
dip your toes in to say, this issomething I want to learn, and
figure out how to do.
D.J. Verret, MD, FACS (13:03):
I was interviewing a friend of mine
from medical school who ended upgoing into hospital
administration. And one of thethings that he said that stuck
with me was, when you're lookingto leave a clinical practice for
some other ground, always gotowards the job, don't run away
from a job. And so I wanted toget your thoughts on that. It
(13:26):
sounds like you were kind ofleaning towards towards that
statement. So I wanted to getyour thoughts on it.
Unknown (13:31):
Yeah, I think that's a beautiful, a beautiful way to
put it. I think with any move,there's a push in a poll, and
you have to make sure thatyou're aware of what, you know,
put the pushes are number one,like why do I want to stop doing
what I'm doing? And that doesn'thave to be a negative. You know,
(13:52):
people tend to think, Oh, youknow, I'm burnt out, I got to
get out. I'm working too manyhours. The pay, you know, too
many people are dying, or, or onthe other end, I'm tired of
taking care of diabetes andhypertension, and I'm bored. You
know, those are all that doesn'thave to be a negative statement.
(14:14):
Right? It's just you're you'reevolving in your life. You're,
you're saying what I was doingfor the last several years is
not what I want to do. And somepeople come to that very
quickly. I had a friend who wasa fellow in oncology back when I
was training, who jumped toindustry in the space of about
(14:36):
two years because he went, youknow what, I made a wrong
decision. I don't want to takecare of cancer patients that
every day, it's too much for meso So recognizing that is a
powerful thing. It's not anegative. That push you that I
think, you know, is not a is nota recognition of defeat. It's a
(15:00):
recognition that your brain isevolving that you're thinking
that differently. In fact, it'snot a defeat, it's actually a
powerful statement that says, Iwant to evolve, and I'm not
going to accept who I am rightnow. And just put in the time,
life's too short to just put inthe time. So you have to find
(15:23):
what you enjoy doing and whatyou're passionate doing. And
whether you switch to an in youknow, biotech or pharma, or to
administration or to working ina law firm, working in patents,
you know, firms working VC, allof those things can be fun, you
just have to find out what'sfun. And, and so what's the poll
(15:45):
is very important. But I thinkeven more important in the
moment is understanding that thepush is not a negative.
D.J. Verret, MD, FACS (15:55):
I think that's also a great expansion on
what my friend was saying, justto be able to recognize where
you want to be in and what youwant to change, because I
totally agree with you. Itlife's too short not to be in a
job that you're happy with. Acouple of the terms you use
biotech versus pharma orbiopharma? Can you kind of
(16:17):
explain the differences in thosebecause I hear those terms a lot
as well.
Unknown (16:23):
Yeah, well, I'm sure there's official definitions, my
definition basically, you know,a biotech a technology company
is generally formed around aparticular idea and is
developing either diagnostics ortherapeutics, based at least
(16:45):
initially on a very narrowideas. So, for example, q
biopharma is an immuno oncologybiotechnology company that was
formed on technology out ofAlbert Einstein to develop
specific molecules that we callimmuno stats that are going to
(17:06):
very selectively deliver anantigen to a protein that T
cells should recognize forcancer therapy, is it at the
same time, it is not developinga targeted agent for diabetes,
for example, it is, you know, ona path based on this, this this
(17:29):
drug platform, and that'simportant. So, biotech tends to
be small, you know, the company,at least early tends to be, you
know, companies with, you know,10 to 100 people that are all
working to get develop agentsaround a particular platform in
a particular disease setting. Asthey get as, as they grow, they
(17:55):
can take on other things, butthey're basically formed around
a specific IP, intellectualproperty and technology. And if
they're, they're oftendeveloping first and human
drugs, doing phase one. Andphase twos. Farm pharma is a,
you know, companies likeNovartis and Bristol Myers are
(18:18):
are large, multi 1000 membercompanies that are developing
drugs and get delivering drugsthat are already approved, as
well as tending to run phasethree trials where they're
trying to develop more drugs. Soyou'll often see if if a company
(18:39):
a biotech company has an agentthat looks promising, they often
get gobbled up, they get boughtby a large company, who will
then do the phase three trials,which often cost hundreds of
millions of dollars. So the wayI think about it is pharma.
pharma is trying to do hasmultiple drugs 10s, if not
(19:02):
hundreds of drugs in theirportfolios across a wide variety
of diseases, and generally areonly running phase three,
generally running phase threestudies as well as giving drugs
to people, you know, byprescription. So
D.J. Verret, MD, FACS (19:18):
what I'd like to use your your
introduction into cue to talk alittle bit about your acting cmo
job and and just the thoughtprocess that goes into
development of a drug trial. Ithink that's extremely
interesting. And also just theprocess for the drug trial,
because people hear a lot aboutphase one, phase two, phase
three, but you don't hear a lotabout all of the work before you
(19:42):
can even start that phase one.
So just to start, can you kindof describe what that pleat pre
clinical work looks like in thedevelopment process, just from a
50,000 foot view?
Unknown (19:56):
Wow. Yeah. Well, that's that's an exciting area. area.
And basically, that's what wedid I did with Q, which was, you
know, developed here we had thisthis molecule that we wanted to,
to give to people. So to do thatyou have to do what are called
ind enabling studies, which areinvestigational new drug
(20:18):
studies. And that includesdeveloping all the assays,
outside of animals or peoplethat demonstrate that your drug
has activity, for example, doesit bind to a T cell in a ditch,
and then you have to do in vivostudies in in in basically in
(20:41):
mice and in in rats to say, Oh,we have anti cancer activity.
And then you have to do what'scalled tox, colic toxicology
studies, where you have to provethat your drug was through a
variety of doses is going to besafe for rats, as well as
(21:02):
potentially dogs or monkeys, anddemonstrate, and not only that
the drug should be safe. Butdetermine the starting dose for
your drug in humans through aset of complex formulas that are
complex, but easily learnable.
You then take that in package,and simultaneously, you're
(21:24):
developing your drug, you'reputting it into vials under good
manufacturing processes, to beable to say that it's sterile
and not has the right pH and theright you the right vehicle that
you can actually give it topeople, whether it's IV or
(21:45):
orally. And then as you're doingall those studies in parallel,
you are also writing it all outand developing what's called the
investigational new drugpackage, where you will present
that whole body of evidence tothe Food and Drug Administration
to say, let us give this topeople. It's a really exciting
(22:08):
process.
D.J. Verret, MD, FACS (22:13):
When and then once you give it to the
FDA, the FDA hopefully will tellyou, okay, you can give it to
people. But that's also thestart of another whole process.
Because the drug design in thatphase one is is actually pretty
important, right?
Ken Pienta, MD (22:31):
Yeah.
Unknown (22:33):
Right, so so once, as part of that package, you have
to develop a phase one trialdesign. Yet generally, there are
multiple phase one trialdesigns. But the most common is
what's called the three by threedesign where you give three
people a drug at a first dose,if it's safe, you then move you
(22:56):
move up the dose and give it toanother three. And if it's safe,
you give it to another three.
But if you find one, got oneperson gets sick, then you out
of those three, enroll threemore people. It's a it's a well
known design that's beendeveloped over the last 20 years
that almost all phase one drugsuse. And that's, again, it's all
(23:16):
about determining safety anddetermining your ultimate dose
for the next set of trials,phase two, where you're actually
trying to determine efficacy.
D.J. Verret, MD, FACS (23:32):
But when you talk about the phase one, I
know with q in particular, younot only you're giving it to the
patients, but you're looking atdata on the back end as well. To
not only determine safety, butto try to get some information
about how the drug works.
Correct. Yeah,
Unknown (23:48):
yeah. Sorry. I didn't realize that's what you were
looking for. Yes. So with withwhenever you're getting a drug
for the first time, you alsolook for two other effects
pharmacokinetic effects or PK?
Which is how fast is your drug?
Get clear the system? Does it doit through the liver does do it
through the kidney? What Howlong does it stay in the blood?
(24:13):
Those kinds of questions, thosepharmacology questions. The
other thing that we're doing isyou draw blood, so you have to
draw blood from the patient anddetermine that and get tissue
from them if you can. And theother part of that is the PD or
pharmacodynamic effects, whichis where gosh, you know, we're
trying to turn on antigenspecific T cells. So we're going
(24:36):
to draw blood from patientsafter they've gotten our drug
and from before they got theirour drug and then put their
their blood in with our naive Tcells and see if we turn them
off. And that that is basicallythe pharmacodynamic effects and
(24:58):
and no matter what drug you'redoing. Developing, whether it's
an immunotherapy or a targetedagent, you're always looking for
on the back end from yourpatients, the PK and PD assets.
D.J. Verret, MD, FACS (25:12):
And I also found it interesting that
phase one isn't, you know,people say phase one. And you
may think, Oh, it's it's prettystandard, as you mentioned,
there are different trialdesigns, but also their
different patient populations,you may give your drug to
depending on what kind of drugit is, right?
Unknown (25:30):
Yeah, absolutely. And, and the cancer world as well as
all medicine has really evolvedor about that. They've just
become more precise, right? Soso we only give our drug, for
example, and we had to work withthe FDA for this. We were
targeting HPV positive HumanPapilloma Virus driven cancers,
(25:55):
we could have picked head, neck,cervical, and you know, penile
cancers. And so, we wespecifically, you know, with the
FDA, they said, Let's pick onedisease type, and develop your
drug and one disease type. Andthen as you get your dose move
into other other treatmentgroups, so every time you're
(26:19):
doing a phase one, it used to bethat it was sort of like, oh,
anybody who has nothing, no, nodisease, no drug left to try for
whatever their disease was, wewere going to give them a phase
one agent, because it was allabout just determining the
safety of that drug. That'sreally rare. Now, almost every
(26:42):
agent that's going into clinicaltrial now is around a specific
disease type. Looking at youbecause we want to look worse,
even in the safety population,you're still looking for signal.
Ken Pienta, MD (26:57):
It's it,
D.J. Verret, MD, FACS (26:58):
it's a lot, you know, when I first kind
of started getting involved withthese companies, you think I
always thought, oh, phase one,you just give the drug to
somebody, but there's a lot thatreally goes into it. Where did
you learn through that process?
Did you start as an investigatorfor drug companies? Or was there
some class you took? Or? I mean,how did that evolve? For you?
Ken Pienta, MD (27:23):
Wow, yeah, yeah.
It's, it's, it's what you'realways learning. And, and you
can't be afraid to say what youdon't know. But I, you know,
I've started out first by, youknow, an academic investigator
running trials for companiesdrug because they had drugs I
was interested in and, you know,understanding number one how to
(27:47):
write a clinical trial. And thatis something, you know, you you
learn through training, althoughthere are classes for it also.
But the classic way back when Iwas doing it, you know, was
here, go, right, this trial,here's a previous example,
right? But there, you know, it'sall on the web now, right. And
(28:08):
then there's a lot of all thematerials of how to what you
need to do to develop a drug isall available from the like, the
FDA websites. And then I alsostarted to consult for companies
and understand, you know, asthey were developing there, as I
was an investigator, they wouldask me to come to an
investigator meeting, and Iwould see the process they used
(28:29):
to get there. And as I wanted tolearn more about that, I would
ask them questions and ask,could I be involved in that in
any way so that I could learnthe processes by which you go to
the FDA, how you put together anind package. And then again,
lots of reading lots oflearning, there's papers on
(28:53):
this, there's books on it,there's websites on all this,
and then every time we hit a,you know, sort of a roadblock of
knowledge, you just, you canfind the answers out there. And,
and so it gets and it getseasier every time but also every
drug has a little bit of adifferent, you know, weight that
(29:14):
needs to be developed. But forexample, the the tox studies are
our standard, pretty muchstandard across the industry.
You got to do two species, yougot to do a rat and a monkey or
a rat and a dog, you know itand, and so what you sort of do
it once and it's like a bike,you know, you just have to plug
(29:36):
your dragon and do it.
D.J. Verret, MD, FACS (29:40):
But I think the the important take
home is it was an evolutionaryprocess for you. It wasn't like
you woke up one day andcongratulations, you're acting
CMO of a company.
Ken Pienta, MD (29:51):
Absolutely correct. Yeah.
D.J. Verret, MD, FACS (29:53):
What one one quick thing we didn't talk
about in that phase processafter you get your FDA approval.
That's also part of theregulatory process, you still
have to get if you stopped toget IRB approval at each one of
your institutions as well, whichis a whole nother process that
involves more physicians,correct?
Unknown (30:14):
Yeah. So as we in, for example, for the FDA approval,
and then, you know, you have towrite the first write the the
IRB template, so we have towrite an IRB template. And we
also have to write aninvestigators brochure. And we
have to write a pharmacy manual.
So there's three pieces of largepieces of work there, that
(30:36):
you've written, the trial thatyou want to do, the IRB, that
consent that goes with it, theinvestigators brochure that goes
with it, which is sort of like adrug insert, and then the
pharmacology manual, which ishow you want them to give the
drug. So you write all of thoseand you submit them to every
place that you want to do thetrial. They then modify it to
(30:59):
their individual idiosyncrasies,which is a good way to put it.
It's each institution and eachIRB has their own
idiosyncrasies, and, and that'show that process works.
D.J. Verret, MD, FACS (31:16):
Ken, this has been fascinating. I really
appreciate the insight into Iwon't use the term non clinical
medicine, just hire clinicalmedicine, but it really
appreciate the time. Thanks forcoming on.
Ken Pienta, MD (31:28):
Yeah, you bet.
Take care.
D.J. Verret, MD, FACS (31:30):
We've been talking with Dr. Ken
Pienta, professor of neurologyand oncology at Johns Hopkins
and acting chief medical officerof Cue Biopharma. You're listeni
g to ask me MD medical school fr the real world. I'm Dr.
J Verret. Thanks for joining u. Until next time, make it
n awesome wee
Announcer (31:49):
Thank you for joining us for another episode of Ask me
MD medical school for the realworld with Dr. DJ Verret if you
ave a question or an idea for ahow, send us an email at
uestions at Ask Me MD pocast.com.
Ask me MD medical school for the real world with
(00:03):
the MD Dr. DJ Verret
D.J. Verret, MD, FAC (00:06):
Greetings, and welcome to another edition
of Ask me MD medical school forthe real world. I'm Dr. DJ
Verret and today we're talkingwith Dr. Ken Pienta, professor
of oncology in urology at JohnsHopkins University and acting
chief medical officer of Qbiopharma about his experience
in academics and pharmaceuticalmedicine. We'll talk to Ken
(00:29):
right after this
Announcer (00:30):
Ask Me MD medical school for the real world.
D.J. Verret, MD, FAC (00:52):
Commerical Here Welcome back to ask me MD
(01:14):
medical school for the realworld. I'm Dr. D.J. Verret. And
today we have the great pleasureof talking with Dr. Ken Pienta,
professor of neurology andoncology at Johns Hopkins and
acting CMO of Cue Biopharma.
Ken, thanks for joining us.
Ken Pienta, MD (01:31):
I'm glad to be here. Thanks for inviting me.
D.J. Verret, MD, FACS (01:34):
So for all of our listeners out there
who may not know, can you giveus a little bit of history of
your background and kind of howyou got where you are today?
Ken Pienta, MD (01:43):
Sure, I trained in internal medicine at the
University of Chicago and thenwent on to do an oncology
fellowship at Johns Hopkins. Andafter that, I moved as an
assistant professor to WayneState, and then the University
of Michigan where I spent 20years running a translational
(02:03):
research lab, basically focusedon prostate cancer metastasis
and therapeutics, and at thesame time building up a practice
in advanced prostate cancer. Andthen after 20 years of doing
that, at the University ofMichigan, I moved to Johns
Hopkins, where I directedstarted to direct urology
(02:24):
research, as well as develop theprecision medicine program for
Johns Hopkins. And that bringsus here to today.
D.J. Verret, MD, FACS (02:35):
For for folks out there that may or may
not really understand could youkind of explain what precision
medicine is. I hear that term alot. But I don't know if
anyone's ever succinctlyexplained it to me.
Unknown (02:49):
Well, their their precision medicine is, you know,
to use the tried and truedefinition is treating the right
patient with the right drug atthe right time. And now in 2020
at the right place. And that'sespecially true now with COVID.
In that we have found that weneed to be much smarter about
(03:12):
how we treat people and where wetreat people do we really need
to bring them into the hospitalto treat them. So part of
precision is actually developingmethods to do video medicine
when it's appropriate andunderstanding when it's not
appropriate. That's all aboutprecision.
D.J. Verret, MD, FACS (03:32):
That's an interesting evolution. I hadn't
thought about the the rightplace. But but it continues, I
recently interviewed the CEO ofa mostly rural hospital system.
And he brought up the potentialfor virtual hospitals, that
they're starting to talk aboutkind of in line with what you're
you're talking about?
Unknown (03:51):
Yes.
D.J. Verret, MD, FACS (03:52):
What what kind of drew you to academic
medicine? Why did you why'd youwant to go in academics over
some other practice opportunity?
Unknown (04:01):
Well, for me, I loved the research. And I loved the
bench research part of it, thetranslation, and so to be
successful, and that what Iunderstood very early, was that
I was going to have to narrow myclinical focus that it was going
(04:22):
to if I was going to studyprostate cancer in the lab,
which is what I was trained todo. It made the most sense to
work with prostate cancerpatients, and therefore they
became my clinical laboratory.
And I would seamlessly do what Iwould look at what I was doing
in the lab and then apply thatto my patients in the clinic as
I tried to develop therapies andthen I would use their blood and
(04:45):
bone marrow and biospecimens andtissue to take back to the lab
to help me do better researchand then as I was developing
those resources programs, Irealized it was very difficult
to take any type of research,whether it be predictive
(05:07):
biomarkers or clinicaltherapeutics, all the way across
the finish line to an FDAapproved product that would help
actually help people across thatsort of gap. And so they started
working more and more withindustry to to understand and
(05:28):
translate what we were doing inthe lab, to patients, and then
from patients clinical trials,all the way to approval. And you
can't do that alone anymore,maybe 30 years, 4050 years ago,
you know, you've heard aboutpeople developing drugs at the
(05:48):
bench and then taking them allthe way to to, to the clinic and
beyond. It takes a village, ittakes a team it takes biotech
by, you know, pharma, academiclabs, etc, to do all that entire
translation across the spectrum.
And that's why I started alsoworking over the years with, you
(06:13):
know, biotech and pharma.
D.J. Verret, MD, FACS (06:17):
What do you find most rewarding about
your involvement in the wholedrug design and development
process?
Unknown (06:27):
You know, I find the bottom line is we're here to
help people and to try to make adifference and find ways that
decrease morbidity andmortality. And I find that each
step along the way, on any givenday is really exciting. And I
have the great privilege ofbeing able to do that dance of
(06:51):
of working in the lab, workingin the in the clinic, but then,
through my connections tobiotech, actually develop those
clinical trials into into largemulticenter trials to work
towards FDA approval. And I'vebeen able to do that now in my
(07:13):
life for not only drugs, butalso imaging agents as well as
bio biomarkers. Like forexample, I was the guy that
developed circulating tumorcells for prostate cancer as a
diagnostic marker.
D.J. Verret, MD, FACS (07:34):
When we were talking earlier, I use the
term non clinical medicine,which I think a lot of people
would say, when you're involvedin pharma, you're, you're in a
non clinical job. But But youbrought up a really good point
that, that no, it's not nonclinical. Can you kind of
explain your thoughts on that?
Unknown (07:52):
Yeah, I, you know, I use that we were talking offline
and you use that that term and Itook some umbrage.
D.J. Verret, MD, FACS (08:02):
That's true. I was I was kind of put in
a different way. But yes.
Unknown (08:07):
The reason why is because, you know, we need smart
people in every step of thisprocess of drug development,
and, and what I tell mystudents, my, my PhD students,
my clinical fellows, is thatit's where you find your joy,
but specifically, you know, forMDS, we need MDS who are trained
(08:33):
to take care of people whounderstand illness, who
recognize side effects, to workin industry, whether that's
biotech or pharma, as we developdrugs, so, for example, is to be
a medical director or a medicalmonitor, for a clinical trial of
(08:53):
a first inhuman drug requires,you know, that you have
expertise, that you canrecognize what side effects are,
and that you can recognize whenyour first inhuman drug might be
having an adverse side effect oradverse event. And that's it. So
(09:14):
you're you're taking care ofpeople, and you're watching the
drug develop. And you're and youAlthough you're not laying your
hands on them, you are directlyinvolved in their care, you are
making lifetime decisions aboutwhether they should continue on
a drug. You know, the recenthalt of the of the Merck study
(09:38):
with COVID is because there wasan MD in pharma. Not seeing
patients but recognizing thatthere was a weird side effect.
That that is that is clinicalmedicine to me. And I think
folks who are switching over toindustry potentially from
(09:58):
academics or from privatePractice to industry, because
they they just don't want to dofor example, the day to day
clinical patient caridy anymore.
They can, that's a veryrewarding track to to be able to
take care of people that way.
D.J. Verret, MD, FACS (10:19):
With your experience kind of being on the
clinical side, the academicside, and then the pharma side
now as an acting cmo with a witha biotech company in clinical
trials, what advice would yougive to physicians that may be
looking to transition into someof these pharmaceutical jobs?
Unknown (10:38):
Yeah, my, my, I guess my number one piece of advice is
to really clearly determine foryourself, what what you're
interested in doing what you'reexcited to do every day. And
they're the spectrum of, forexample, biotech. That means
(11:01):
that, you know, are you moreinterested in immunology? Are
you more interested inRheumatology? Are you more, you
know, find fight, you can findthere's so many companies out
there. And so manyopportunities, you can really
find the type of position thatyou want to with the kind of
drug you want to if you want tojust dabble, you know, to say,
(11:24):
is this interesting to me, thatmany of these companies have
advisory boards that you canbecome involved in as they try
to develop agents and they'relooking for a, for example, how
will this drug be used in theclinical practice you were in?
Whether and it doesn't matterwhether that was academics, or
(11:45):
private practice or largegroups, there's a lot of
opportunity there. The otherthing you have to think about
is, do you want to be inbiotech, which tends to be a
small, you know, smallerorganizations where you're going
to be the MD, and they're goingto be looking at you for your
for clinical acumen. Andunderstanding how a drug affects
(12:09):
patients. Where or do you wantto be part of a larger
organization, like a pharma, abig drug company, where you
might be asked to, you know,develop a particular agent
across multiple countries or doit, you know, we already know
the toxicities and what theyneed somebody to run a phase
three, study. The, the also, theother thing you can do is, you
(12:35):
know, depending on yourtraining, you can get involved
in, quite frankly, on the nonclinical side, do you want to
develop help develop FDApackages, you know, the the ind
investigational new drugpackages. And to do that, again,
you can there, there are ways todo that, where you can sort of
(12:57):
dip your toes in to say, this issomething I want to learn, and
figure out how to do.
D.J. Verret, MD, FACS (13:03):
I was interviewing a friend of mine
from medical school who ended upgoing into hospital
administration. And one of thethings that he said that stuck
with me was, when you're lookingto leave a clinical practice for
some other ground, always gotowards the job, don't run away
from a job. And so I wanted toget your thoughts on that. It
(13:26):
sounds like you were kind ofleaning towards towards that
statement. So I wanted to getyour thoughts on it.
Unknown (13:31):
Yeah, I think that's a beautiful, a beautiful way to
put it. I think with any move,there's a push in a poll, and
you have to make sure thatyou're aware of what, you know,
put the pushes are number one,like why do I want to stop doing
what I'm doing? And that doesn'thave to be a negative. You know,
(13:52):
people tend to think, Oh, youknow, I'm burnt out, I got to
get out. I'm working too manyhours. The pay, you know, too
many people are dying, or, or onthe other end, I'm tired of
taking care of diabetes andhypertension, and I'm bored. You
know, those are all that doesn'thave to be a negative statement.
(14:14):
Right? It's just you're you'reevolving in your life. You're,
you're saying what I was doingfor the last several years is
not what I want to do. And somepeople come to that very
quickly. I had a friend who wasa fellow in oncology back when I
was training, who jumped toindustry in the space of about
(14:36):
two years because he went, youknow what, I made a wrong
decision. I don't want to takecare of cancer patients that
every day, it's too much for meso So recognizing that is a
powerful thing. It's not anegative. That push you that I
think, you know, is not a is nota recognition of defeat. It's a
(15:00):
recognition that your brain isevolving that you're thinking
that differently. In fact, it'snot a defeat, it's actually a
powerful statement that says, Iwant to evolve, and I'm not
going to accept who I am rightnow. And just put in the time,
life's too short to just put inthe time. So you have to find
(15:23):
what you enjoy doing and whatyou're passionate doing. And
whether you switch to an in youknow, biotech or pharma, or to
administration or to working ina law firm, working in patents,
you know, firms working VC, allof those things can be fun, you
just have to find out what'sfun. And, and so what's the poll
(15:45):
is very important. But I thinkeven more important in the
moment is understanding that thepush is not a negative.
D.J. Verret, MD, FACS (15:55):
I think that's also a great expansion on
what my friend was saying, justto be able to recognize where
you want to be in and what youwant to change, because I
totally agree with you. Itlife's too short not to be in a
job that you're happy with. Acouple of the terms you use
biotech versus pharma orbiopharma? Can you kind of
(16:17):
explain the differences in thosebecause I hear those terms a lot
as well.
Unknown (16:23):
Yeah, well, I'm sure there's official definitions, my
definition basically, you know,a biotech a technology company
is generally formed around aparticular idea and is
developing either diagnostics ortherapeutics, based at least
(16:45):
initially on a very narrowideas. So, for example, q
biopharma is an immuno oncologybiotechnology company that was
formed on technology out ofAlbert Einstein to develop
specific molecules that we callimmuno stats that are going to
(17:06):
very selectively deliver anantigen to a protein that T
cells should recognize forcancer therapy, is it at the
same time, it is not developinga targeted agent for diabetes,
for example, it is, you know, ona path based on this, this this
(17:29):
drug platform, and that'simportant. So, biotech tends to
be small, you know, the company,at least early tends to be, you
know, companies with, you know,10 to 100 people that are all
working to get develop agentsaround a particular platform in
a particular disease setting. Asthey get as, as they grow, they
(17:55):
can take on other things, butthey're basically formed around
a specific IP, intellectualproperty and technology. And if
they're, they're oftendeveloping first and human
drugs, doing phase one. Andphase twos. Farm pharma is a,
you know, companies likeNovartis and Bristol Myers are
(18:18):
are large, multi 1000 membercompanies that are developing
drugs and get delivering drugsthat are already approved, as
well as tending to run phasethree trials where they're
trying to develop more drugs. Soyou'll often see if if a company
(18:39):
a biotech company has an agentthat looks promising, they often
get gobbled up, they get boughtby a large company, who will
then do the phase three trials,which often cost hundreds of
millions of dollars. So the wayI think about it is pharma.
pharma is trying to do hasmultiple drugs 10s, if not
(19:02):
hundreds of drugs in theirportfolios across a wide variety
of diseases, and generally areonly running phase three,
generally running phase threestudies as well as giving drugs
to people, you know, byprescription. So
D.J. Verret, MD, FACS (19:18):
what I'd like to use your your
introduction into cue to talk alittle bit about your acting cmo
job and and just the thoughtprocess that goes into
development of a drug trial. Ithink that's extremely
interesting. And also just theprocess for the drug trial,
because people hear a lot aboutphase one, phase two, phase
three, but you don't hear a lotabout all of the work before you
(19:42):
can even start that phase one.
So just to start, can you kindof describe what that pleat pre
clinical work looks like in thedevelopment process, just from a
50,000 foot view?
Unknown (19:56):
Wow. Yeah. Well, that's that's an exciting area. area.
And basically, that's what wedid I did with Q, which was, you
know, developed here we had thisthis molecule that we wanted to,
to give to people. So to do thatyou have to do what are called
ind enabling studies, which areinvestigational new drug
(20:18):
studies. And that includesdeveloping all the assays,
outside of animals or peoplethat demonstrate that your drug
has activity, for example, doesit bind to a T cell in a ditch,
and then you have to do in vivostudies in in in basically in
(20:41):
mice and in in rats to say, Oh,we have anti cancer activity.
And then you have to do what'scalled tox, colic toxicology
studies, where you have to provethat your drug was through a
variety of doses is going to besafe for rats, as well as
(21:02):
potentially dogs or monkeys, anddemonstrate, and not only that
the drug should be safe. Butdetermine the starting dose for
your drug in humans through aset of complex formulas that are
complex, but easily learnable.
You then take that in package,and simultaneously, you're
(21:24):
developing your drug, you'reputting it into vials under good
manufacturing processes, to beable to say that it's sterile
and not has the right pH and theright you the right vehicle that
you can actually give it topeople, whether it's IV or
(21:45):
orally. And then as you're doingall those studies in parallel,
you are also writing it all outand developing what's called the
investigational new drugpackage, where you will present
that whole body of evidence tothe Food and Drug Administration
to say, let us give this topeople. It's a really exciting
(22:08):
process.
D.J. Verret, MD, FACS (22:13):
When and then once you give it to the
FDA, the FDA hopefully will tellyou, okay, you can give it to
people. But that's also thestart of another whole process.
Because the drug design in thatphase one is is actually pretty
important, right?
Ken Pienta, MD (22:31):
Yeah.
Unknown (22:33):
Right, so so once, as part of that package, you have
to develop a phase one trialdesign. Yet generally, there are
multiple phase one trialdesigns. But the most common is
what's called the three by threedesign where you give three
people a drug at a first dose,if it's safe, you then move you
(22:56):
move up the dose and give it toanother three. And if it's safe,
you give it to another three.
But if you find one, got oneperson gets sick, then you out
of those three, enroll threemore people. It's a it's a well
known design that's beendeveloped over the last 20 years
that almost all phase one drugsuse. And that's, again, it's all
(23:16):
about determining safety anddetermining your ultimate dose
for the next set of trials,phase two, where you're actually
trying to determine efficacy.
D.J. Verret, MD, FACS (23:32):
But when you talk about the phase one, I
know with q in particular, younot only you're giving it to the
patients, but you're looking atdata on the back end as well. To
not only determine safety, butto try to get some information
about how the drug works.
Correct. Yeah,
Unknown (23:48):
yeah. Sorry. I didn't realize that's what you were
looking for. Yes. So with withwhenever you're getting a drug
for the first time, you alsolook for two other effects
pharmacokinetic effects or PK?
Which is how fast is your drug?
Get clear the system? Does it doit through the liver does do it
through the kidney? What Howlong does it stay in the blood?
(24:13):
Those kinds of questions, thosepharmacology questions. The
other thing that we're doing isyou draw blood, so you have to
draw blood from the patient anddetermine that and get tissue
from them if you can. And theother part of that is the PD or
pharmacodynamic effects, whichis where gosh, you know, we're
trying to turn on antigenspecific T cells. So we're going
(24:36):
to draw blood from patientsafter they've gotten our drug
and from before they got theirour drug and then put their
their blood in with our naive Tcells and see if we turn them
off. And that that is basicallythe pharmacodynamic effects and
(24:58):
and no matter what drug you'redoing. Developing, whether it's
an immunotherapy or a targetedagent, you're always looking for
on the back end from yourpatients, the PK and PD assets.
D.J. Verret, MD, FACS (25:12):
And I also found it interesting that
phase one isn't, you know,people say phase one. And you
may think, Oh, it's it's prettystandard, as you mentioned,
there are different trialdesigns, but also their
different patient populations,you may give your drug to
depending on what kind of drugit is, right?
Unknown (25:30):
Yeah, absolutely. And, and the cancer world as well as
all medicine has really evolvedor about that. They've just
become more precise, right? Soso we only give our drug, for
example, and we had to work withthe FDA for this. We were
targeting HPV positive HumanPapilloma Virus driven cancers,
(25:55):
we could have picked head, neck,cervical, and you know, penile
cancers. And so, we wespecifically, you know, with the
FDA, they said, Let's pick onedisease type, and develop your
drug and one disease type. Andthen as you get your dose move
into other other treatmentgroups, so every time you're
(26:19):
doing a phase one, it used to bethat it was sort of like, oh,
anybody who has nothing, no, nodisease, no drug left to try for
whatever their disease was, wewere going to give them a phase
one agent, because it was allabout just determining the
safety of that drug. That'sreally rare. Now, almost every
(26:42):
agent that's going into clinicaltrial now is around a specific
disease type. Looking at youbecause we want to look worse,
even in the safety population,you're still looking for signal.
Ken Pienta, MD (26:57):
It's it,
D.J. Verret, MD, FACS (26:58):
it's a lot, you know, when I first kind
of started getting involved withthese companies, you think I
always thought, oh, phase one,you just give the drug to
somebody, but there's a lot thatreally goes into it. Where did
you learn through that process?
Did you start as an investigatorfor drug companies? Or was there
some class you took? Or? I mean,how did that evolve? For you?
Ken Pienta, MD (27:23):
Wow, yeah, yeah.
It's, it's, it's what you'realways learning. And, and you
can't be afraid to say what youdon't know. But I, you know,
I've started out first by, youknow, an academic investigator
running trials for companiesdrug because they had drugs I
was interested in and, you know,understanding number one how to
(27:47):
write a clinical trial. And thatis something, you know, you you
learn through training, althoughthere are classes for it also.
But the classic way back when Iwas doing it, you know, was
here, go, right, this trial,here's a previous example,
right? But there, you know, it'sall on the web now, right. And
(28:08):
then there's a lot of all thematerials of how to what you
need to do to develop a drug isall available from the like, the
FDA websites. And then I alsostarted to consult for companies
and understand, you know, asthey were developing there, as I
was an investigator, they wouldask me to come to an
investigator meeting, and Iwould see the process they used
(28:29):
to get there. And as I wanted tolearn more about that, I would
ask them questions and ask,could I be involved in that in
any way so that I could learnthe processes by which you go to
the FDA, how you put together anind package. And then again,
lots of reading lots oflearning, there's papers on
(28:53):
this, there's books on it,there's websites on all this,
and then every time we hit a,you know, sort of a roadblock of
knowledge, you just, you canfind the answers out there. And,
and so it gets and it getseasier every time but also every
drug has a little bit of adifferent, you know, weight that
(29:14):
needs to be developed. But forexample, the the tox studies are
our standard, pretty muchstandard across the industry.
You got to do two species, yougot to do a rat and a monkey or
a rat and a dog, you know itand, and so what you sort of do
it once and it's like a bike,you know, you just have to plug
(29:36):
your dragon and do it.
D.J. Verret, MD, FACS (29:40):
But I think the the important take
home is it was an evolutionaryprocess for you. It wasn't like
you woke up one day andcongratulations, you're acting
CMO of a company.
Ken Pienta, MD (29:51):
Absolutely correct. Yeah.
D.J. Verret, MD, FACS (29:53):
What one one quick thing we didn't talk
about in that phase processafter you get your FDA approval.
That's also part of theregulatory process, you still
have to get if you stopped toget IRB approval at each one of
your institutions as well, whichis a whole nother process that
involves more physicians,correct?
Unknown (30:14):
Yeah. So as we in, for example, for the FDA approval,
and then, you know, you have towrite the first write the the
IRB template, so we have towrite an IRB template. And we
also have to write aninvestigators brochure. And we
have to write a pharmacy manual.
So there's three pieces of largepieces of work there, that
(30:36):
you've written, the trial thatyou want to do, the IRB, that
consent that goes with it, theinvestigators brochure that goes
with it, which is sort of like adrug insert, and then the
pharmacology manual, which ishow you want them to give the
drug. So you write all of thoseand you submit them to every
place that you want to do thetrial. They then modify it to
(30:59):
their individual idiosyncrasies,which is a good way to put it.
It's each institution and eachIRB has their own
idiosyncrasies, and, and that'show that process works.
D.J. Verret, MD, FACS (31:16):
Ken, this has been fascinating. I really
appreciate the insight into Iwon't use the term non clinical
medicine, just hire clinicalmedicine, but it really
appreciate the time. Thanks forcoming on.
Ken Pienta, MD (31:28):
Yeah, you bet.
Take care.
D.J. Verret, MD, FACS (31:30):
We've been talking with Dr. Ken
Pienta, professor of neurologyand oncology at Johns Hopkins
and acting chief medical officerof Cue Biopharma. You're listeni
g to ask me MD medical school fr the real world. I'm Dr.
J Verret. Thanks for joining u. Until next time, make it
n awesome wee
Announcer (31:49):
Thank you for joining us for another episode of Ask me
MD medical school for the realworld with Dr. DJ Verret if you
ave a question or an idea for ahow, send us an email at
uestions at Ask Me MD pocast.com.
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