April 9, 2025 • 24 mins
This week on BioTech Nation, Dr. Thomas Chen, Director of Neuro-Oncology at USC and Founder of NeOnc Technologies, shares treating glioblastoma by delivering a drug directly to the brain through nasal inhalation changes the drug delivery game, bypassing the blood-brain barrier. This technique is achieving results in clinical trials.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Moira Gunn (00:11):
Glioblastoma, brain cancer, one of the biggest
challenges to effectivelytreating it is simply getting
drugs to the brain. Today,Doctor. Thomas Chen, the
director of neuro oncology atUSC and founder, CEO, and chief
scientific officer of NeOncTechnologies tells us about the
(00:34):
scientific journey of a new wayof delivering drugs to the
brain. Doctor Chen, welcome tothe program.
Dr. Thomas Chen (00:42):
Thank you so much.
Dr. Moira Gunn (00:44):
Now you're going to take us on quite a journey
today, but I wanna start with alook at our current situation
independent of that journey. Andtoday, we're gonna be talking
about brain cancer. And as yousay, brain cancer is a disease
of the brain, and we allunderstand at various levels
(01:04):
that it's hard to get drugs tothe brain. We always hear about
the blood brain barrier. And, sowhether your drug is a pill or
an IV drug that goes into yourbloodstream, it has the
challenge of getting to thebrain.
How has that stymied the searchfor drugs to treat brain cancer?
Dr. Thomas Chen (01:24):
So, when we talk about treatment, basically
we're talking about how do wedeliver the drug appropriately
to the target, in this case it'sthe brain cancer. And then once
it gets to the target, does ithave good activity? And so those
are the two things that we needto address when we talk about
(01:45):
any sort of developing anytreatment, new treatment
modalities for brain cancer.Now, the first part, getting
drugs to the brain, that's thepart that you've been
addressing. And what I can tellyou is this, we have many drugs
(02:06):
that actually work pretty wellon cancer cells.
And they have one problem, isthat they cannot get to the
brain. Now, in terms of gettingto the brain, if you are what we
call water soluble, watersoluble means that it dissolves
(02:28):
well in water, so you can giveit like intravenously or orally,
it goes in the bloodstream.Those types of molecules do not
cross the blood brain barriervery well. In fact, the types of
molecules that cross the bloodbrain barrier well are the ones
(02:49):
that are said to be lipophilic,which means that they're fatty
and they can cross the bloodbrain barrier better. And so
many therapeutics, many people,are working towards developing
drugs that can cross the bloodbrain barrier better by making
(03:14):
them more lipophilic.
Now there are actually peoplealso looking at, receptors that
level the blood brain barrier tosee if their drug can bind to a
receptor and let that receptorcarry it across the blood brain
barrier. So there's lots of veryfascinating, work that very
(03:40):
smart people are doing to try toget across the blood brain
barrier to the target. We'restill having a lot of trouble
with it.
Dr. Moira Gunn (03:49):
So the barrier's the barrier.
Dr. Thomas Chen (03:51):
Barrier's the barrier, yes.
Dr. Moira Gunn (03:53):
Now let's get to your journey, and where do we
start? And I wanted to start bytalking about a naturally
occurring molecule, which you'vetold me about, that we call POH,
perilyl alcohol. What has POHgot to do with anything?
Dr. Thomas Chen (04:12):
Actually, para alcohol was, first worked upon
by an American biochemist. Hewas a professor of biochemistry
at University of Wisconsin. Hisname was Michael Gold. And
unfortunately Michael Gould has,passed away. But what he did was
(04:34):
that he was working on thismolecule called para alcohol.
It's actually a naturalderivative. It's isolated from,
citrus fruit, and you can alsoget it from cherries. Michael
Gold found that para alcohol,when he added to his cancer
(04:56):
cells that were dividing inculture, was a very good cell
cycle inhibitor, meaning that itinhibited the cell from dividing
further. And using thatknowledge, what he and his
colleagues did was that theydeveloped a formulation for the
peri alcohol, and they tested itin cancer patients. Now what
(05:19):
they did was that they tested itin patients with colon cancer,
they tested it in patients withbreast cancer, but they tested
in, these patients up to phasetwo.
And what they found was that,yes, the peri alcohol did have
an effect on the cancer cells,but the problem was that it had
(05:41):
a lot of systemic side effectswhen you give it orally. But it
was just poorly tolerated. Andin terms of how it affected the
cancer, it was also not as wellas they would have liked to be.
And as a result, what happenedwas that the para alcohol was
(06:01):
then stopped from the standpointof treatment. And what happened
then was that one of mycolleagues, his name is Clovis
Fonsacop.
Clovis is a neurosurgeon fromRio De Janeiro in Brazil. And,
he's kind of an out of the boxthinker. And he went to,
(06:23):
University of Wisconsin and he,Michael Gold was telling him
about para alcohol and Clovisthought, Hey, you know, that
sounds like an interesting drugfor maybe treating brain cancer.
And Michael gave him a jug ofpara alcohol.
Dr. Moira Gunn (06:41):
Just a jug, like a thermos of
Dr. Thomas Chen (06:43):
Yeah, like a big container. Clovis, at that
time there was no TSA oranything, and Clovis just lugged
it home to Rio De Janeiro. Andso he thought that, I'm a
neurosurgeon, I would like totry on my brain cancer patients.
(07:04):
But at that time, a newprocedure for delivery to the
brain was actually gettingdeveloped in animal models, and
that's called a nasal braindelivery. And the whole concept
of the nasal brain delivery wasthat instead of trying to go
through the blood brain barriersystemically, what you're trying
(07:28):
to do is now deliver, you'rebypassing the blood brain
barrier, and you're deliveringthe drug via the cranial nerves.
And what people found in theanimal models is that there are
two cranial nerves that areparticularly important for nasal
brain delivery. And the firstcranial nerve, I think everybody
(07:50):
knows, is what's called theolfactory nerve. That's the
nerve related to smell. And whatthey found was that in these
patients with the olfactorynerve, that the olfactory nerve
was a very good conduit fordelivery of molecules to the
brain. This is what they foundin animal models.
(08:11):
And also the fifth cranial nerveis the one that's involved with
sensation to the face andability to chew. And so this
sensation of face, the fifthcranial nerve, is also
associated with the nasal braindelivery. So here's the thing.
So Clovis thought that, hey, youknow, so could you bypass that
(08:34):
oral side effect by inhaling itwith the nasal brain delivery?
So the drug, instead of havingto go through your whole body
system to get to the brain,could you just inhale that drug
and take it up to the brain andhave an effect in the brain
cancer?
And so Clovis started treatingpatients. And so what happened
(08:58):
was that he treated about 300patients and these patients had
basically almost no sideeffects. And on top of that,
some of these patients actuallyhad long term survival and their
tumors actually got smaller. Andthis was like, you know, for us,
(09:19):
it's like when we see a braintumor getting smaller on
imaging, that's like a home run.And so Clovis presented his data
to the Brazilian NeurosurgicalSociety.
And he won first place that yearfor that. And because of that,
he won the first place prize wasthat he could go to any lab that
(09:43):
he chose and work there as partof, and he would be granted a
stipend basically. And so hechose to come to USC and work
with me.
Dr. Moira Gunn (09:55):
He chose your lab, that was the prize.
Dr. Thomas Chen (09:58):
He chose my lab, that's right. And when he
came, he was so excited abouthis work. He showed me his MRI
scans and, you know, he reallyhad like patients that had very
large brain tumors, get smalleron further imaging. And I told
(10:19):
Clovis, I said, Well, if this isas good as you say it is, how
come nobody else in the world isdoing this? And I said that,
Well, you know, what we shoulddo is that we should do a
validation study in The UnitedStates and we should, run it
through several academic centershere and see if we can get the
(10:42):
same results you do.
Now, at that time, I wasthinking, okay, so in order for
me to get this drug out to astage where I can do a clinical
trial, where I can get an INDapproved, that all requires
money. Okay? And so I toldClovis that what we need to do
(11:04):
is that we should form a companyand we should, get IP for the
compound And then we shouldapply to the FDA for an IND,
which is Investigational NewDrug, and see if we can, raise
some money from the companyhaving some property and then
(11:26):
run a clinical trial. So thatwas our plan. So then what I did
was that I went to, USC and we,put together a patent.
And the patent was basically forthe use of para alcohol for
treatment of brain cancer. But Itold Clovis that para alcohol is
(11:48):
a commercially availablecompound. And therefore, there
would not be any sort ofintellectual property aside from
the fact that you're now usingit for intranasal delivery. So
what we did was that we went toa local chemistry lab and we
(12:10):
asked the question, can we makethat per alcohol purer than what
it is now? And so what we didwith our local chemistry
company, and they're calledNorac Pharma, is that we asked
the question, could we purifythis?
And could we purify this underGMP or good manufacturing
(12:32):
practice conditions? And youneed to have a drug to be GMP ed
in order to be used in humanpatients. And so, what we were
able to do is that we were ableto add a purification stuff to
this chemical per alcohol, andwe made it into 99.6% pure. And
(12:55):
it was done under GMPconditions. And after we had
done that, we went to the FDAand we wrote a patent for this
purification process.
And we got the patent granted.And then not only the patent
granted, but we also applied fororphan drug status for this
(13:19):
drug, and we also applied forfast track status. But I think
most importantly is that we hada designation of a new chemical
entity with our purificationstep. We then took this set of
information, and then we wrotean IND for a clinical trial. And
(13:42):
at that time, we wrote it forPhase IPhase IIa, and we
submitted it to the FDA, andthey approved it.
And I think that part of thereason we got approved so
rapidly was because the FDArecognized that we're really
dealing with the disease that'slife and death. And so with
(14:03):
that, then what we then did wasthat we got approved and then we
selected some sites to be inthis trial. And the sites that
were involved was the Universityof Southern California, the
Cleveland Clinic, the Universityof Washington up in Seattle, and
University of Wisconsin. Andwith those sites, we then ran a
(14:28):
clinical trial. Now, what I cantell you from our Phase I
testing was that one, thepatients tolerate very well.
They basically had no sideeffects, just like Clovis was
telling me with his patients inBrazil. Two, they didn't have
any of the common toxicitiesthat you would think from
(14:49):
chemotherapy. They didn't theirbone marrow was absolutely
normal. They didn't lose anyhair. They really didn't have
any nausea, vomiting, and noheadaches from inhaling this
product.
And so the patients actuallytolerated very well and did very
well. Now, what we then did wasthat as we went up the dosing,
(15:13):
we found that basically thisheld through even from the
lowest dosage to the highestdosage. Now, along the way, we
also are monitoring thesepatients in terms of how they're
doing clinically. And so eventhough this is a toxicity trial,
(15:33):
we're still getting our MRIscans every two months and
seeing how the tumor is doing.And what we found was that in
some patients, their tumors gotsmaller after inhalation, after
treatment with this therapy.
And in fact, in one patient, thetumor actually disappeared on
(15:54):
MRI scan. And it's what we calla radiographically complete
remission, when the tumor goesaway in MRI scan. And we had
four patients that actuallylived for longer than three
years. Now, so you can say,well, you know, you only had 12
patients. But the thing is thatthe patient population that we
(16:18):
were treating, we were notexpecting these types of results
because the patient populationwe were treating were patients
that had failed conventionaltherapy.
So these were patients that werewhat we call glioblastoma
patients. So they're the worsttype of patients. Their
prognosis on the whole is abouttwelve to fifteen months after
(16:41):
diagnosis. And so thesepatients, undergo conventional
therapy, which is surgery,radiation, and chemotherapy with
a drug called temozolomide.After they fail that treatment,
then they come to our trial.
(17:01):
And so if you ask me like, well,okay, so if you fail
conventional therapy, how longdo you usually live? And the
answer is that most patientshave a survival time of about
five to six months. So we had,four patients that lived longer
than three years. So thequestion is that what was so
(17:23):
unique about their biology thatthey had such a great response
to our drug. And so what we didwas that we went back to their
tumors, we did genomic analysis,and we actually found that they
had something in common.
And that was an IDH1 mutationwithin their tumor cells. And
(17:45):
having that knowledge, I wentback to the FDA and I said, we
had, even though we weresupposed to run just a phase one
study for toxicity, we have fourpatients that did so much better
than expected. And so for ourphase 2A trial, could we just
enroll patients with IDH1mutations who are what we call
(18:09):
recurrent disease and have amalignant glioma. And the FDA
gave us permission to do that.And that resulted in our current
trial, which is a phase 2A, andwe are now almost nearing the
end of our trial.
We have seven more patients toenroll from that 25 patient
(18:33):
cohort. And then we will be donewith the phase 2A. And from
there, we will have a readout interms of how this drug does in
this population of patients, 25patients, in terms of efficacy,
which is what the phase II issupposed to address.
Dr. Moira Gunn (18:52):
What percentage of glioblastoma patients have
this IDH1 mutation? Do we evenknow?
Dr. Thomas Chen (19:00):
Ah, that's a very good question. So, in the
low grade gliomas, in the gradetwos for example, up to fifty
percent of the patient's tumorcould be IDH1 mutations. Now,
when you move up to a gradethree, that number goes down. So
(19:23):
instead of fifty percent beingpositive, it goes down to about
twenty five percent. And thenwhen you go down to a grade
four, which is the glioblastoma,it could be present in three to
five percent.
And so it is correlated with thegrade of the tumor and the
(19:46):
higher grades have a lowerincidence.
Dr. Moira Gunn (19:49):
Okay. So at this point in
Dr. Thomas Chen (19:51):
the
Dr. Moira Gunn (19:51):
story, you have this phase 2a, you're out of
phase one with just the IDH1mutation. So they're in that
stage one, stage two, glioma.And, but what about the rest of
the people?
Dr. Thomas Chen (20:08):
Ah, okay. So, here's the thing is that, well,
first of all, I want to say thatwith the phase 2A, what we want
to establish is that there isefficacy with our treatment.
Now, what we want to do, becausewe're going to have to do a
(20:29):
phase 2B, And the Phase IIb ismost likely going to be about 70
to 80 patients. And so the PhaseIIb would be a larger cohort of
patients. All patients will begetting treated, unlike a phase
three where sometimes there's aplacebo, group.
(20:52):
But with this phase 2B, whatwe're going to do is that we are
going to recruit all comers.Okay? So whether you have an
IDH1 mutation or you don't havean IDH1 mutation, we're going to
be treating them. And then whatwe will be able to do is answer
exactly your question. If youdon't have an IDH1 mutation, how
(21:18):
does that compare when you havethis larger cohort of patients
IDH1 mutations and no IDH1mutations, what is the overall
efficacy and survival time forall patients?
And then how does it comparebetween the two groups? And so
that's coming up. That'ssomething that we are planning
(21:40):
to do for Phase IIb to answerthat question.
Dr. Moira Gunn (21:44):
So what about everybody else?
Dr. Thomas Chen (21:47):
Well, what would happen if we took a drug
that we know has activityagainst brain cancer and we
chemically bind it to the pairalcohol, could we make a new
compound with differentproperties that may be more
effective? And so what we didwas that we took our standard of
(22:11):
care drug, it's calledtemozolomide or TMZ, and we
chemically para alcohol to it.And then we took this new
compound and we put it throughour blood brain barrier program.
Dr. Moira Gunn (22:27):
And by program, you mean a software program, a
computer program.
Dr. Thomas Chen (22:31):
Software program, exactly, exactly. And
what we found was thattemozolomide does cross the
blood brain barrier, but justnot that well. And so we
conjugated to our alcohol, wefound that it crossed the blood
brain barrier much better.
Dr. Moira Gunn (22:49):
Now I want to go back to the first one you did
when you just were trying thosethat phase one, you had four
cohorts of three patients, andyou were increasing the dosage.
And four patients lived, and oneat the time was continuing to
(23:10):
live. Is that patient stillalive today?
Dr. Thomas Chen (23:13):
Actually that patient is still alive today.
And we still, maintain contactwith that patient. And that
patient, actually, you know, Itold you that we get MRI scans
every two months. And now she's,I think, getting MRI scans every
six months now. And continuingto do well.
Dr. Moira Gunn (23:36):
Well, doctor Chen, this has been terrific. I
hope you come back and see usagain.
Dr. Thomas Chen (23:41):
Yeah. I hope so too. Thank you.
Dr. Moira Gunn (23:44):
Doctor Thomas Chen is the director of neuro
oncology at USC and the Founder,CEO, and CSO of NeOnc
Technologies. Three differentclinical trials in brain cancer
are now recruiting. Moreinformation is available on the
web at neonc.com. That's ne0nc,neonc Com.
Glioblastoma, brain cancer, one of the biggest
challenges to effectivelytreating it is simply getting
drugs to the brain. Today,Doctor. Thomas Chen, the
director of neuro oncology atUSC and founder, CEO, and chief
scientific officer of NeOncTechnologies tells us about the
(00:34):
scientific journey of a new wayof delivering drugs to the
brain. Doctor Chen, welcome tothe program.
Dr. Thomas Chen (00:42):
Thank you so much.
Dr. Moira Gunn (00:44):
Now you're going to take us on quite a journey
today, but I wanna start with alook at our current situation
independent of that journey. Andtoday, we're gonna be talking
about brain cancer. And as yousay, brain cancer is a disease
of the brain, and we allunderstand at various levels
(01:04):
that it's hard to get drugs tothe brain. We always hear about
the blood brain barrier. And, sowhether your drug is a pill or
an IV drug that goes into yourbloodstream, it has the
challenge of getting to thebrain.
How has that stymied the searchfor drugs to treat brain cancer?
Dr. Thomas Chen (01:24):
So, when we talk about treatment, basically
we're talking about how do wedeliver the drug appropriately
to the target, in this case it'sthe brain cancer. And then once
it gets to the target, does ithave good activity? And so those
are the two things that we needto address when we talk about
(01:45):
any sort of developing anytreatment, new treatment
modalities for brain cancer.Now, the first part, getting
drugs to the brain, that's thepart that you've been
addressing. And what I can tellyou is this, we have many drugs
(02:06):
that actually work pretty wellon cancer cells.
And they have one problem, isthat they cannot get to the
brain. Now, in terms of gettingto the brain, if you are what we
call water soluble, watersoluble means that it dissolves
(02:28):
well in water, so you can giveit like intravenously or orally,
it goes in the bloodstream.Those types of molecules do not
cross the blood brain barriervery well. In fact, the types of
molecules that cross the bloodbrain barrier well are the ones
(02:49):
that are said to be lipophilic,which means that they're fatty
and they can cross the bloodbrain barrier better. And so
many therapeutics, many people,are working towards developing
drugs that can cross the bloodbrain barrier better by making
(03:14):
them more lipophilic.
Now there are actually peoplealso looking at, receptors that
level the blood brain barrier tosee if their drug can bind to a
receptor and let that receptorcarry it across the blood brain
barrier. So there's lots of veryfascinating, work that very
(03:40):
smart people are doing to try toget across the blood brain
barrier to the target. We'restill having a lot of trouble
with it.
Dr. Moira Gunn (03:49):
So the barrier's the barrier.
Dr. Thomas Chen (03:51):
Barrier's the barrier, yes.
Dr. Moira Gunn (03:53):
Now let's get to your journey, and where do we
start? And I wanted to start bytalking about a naturally
occurring molecule, which you'vetold me about, that we call POH,
perilyl alcohol. What has POHgot to do with anything?
Dr. Thomas Chen (04:12):
Actually, para alcohol was, first worked upon
by an American biochemist. Hewas a professor of biochemistry
at University of Wisconsin. Hisname was Michael Gold. And
unfortunately Michael Gould has,passed away. But what he did was
(04:34):
that he was working on thismolecule called para alcohol.
It's actually a naturalderivative. It's isolated from,
citrus fruit, and you can alsoget it from cherries. Michael
Gold found that para alcohol,when he added to his cancer
(04:56):
cells that were dividing inculture, was a very good cell
cycle inhibitor, meaning that itinhibited the cell from dividing
further. And using thatknowledge, what he and his
colleagues did was that theydeveloped a formulation for the
peri alcohol, and they tested itin cancer patients. Now what
(05:19):
they did was that they tested itin patients with colon cancer,
they tested it in patients withbreast cancer, but they tested
in, these patients up to phasetwo.
And what they found was that,yes, the peri alcohol did have
an effect on the cancer cells,but the problem was that it had
(05:41):
a lot of systemic side effectswhen you give it orally. But it
was just poorly tolerated. Andin terms of how it affected the
cancer, it was also not as wellas they would have liked to be.
And as a result, what happenedwas that the para alcohol was
(06:01):
then stopped from the standpointof treatment. And what happened
then was that one of mycolleagues, his name is Clovis
Fonsacop.
Clovis is a neurosurgeon fromRio De Janeiro in Brazil. And,
he's kind of an out of the boxthinker. And he went to,
(06:23):
University of Wisconsin and he,Michael Gold was telling him
about para alcohol and Clovisthought, Hey, you know, that
sounds like an interesting drugfor maybe treating brain cancer.
And Michael gave him a jug ofpara alcohol.
Dr. Moira Gunn (06:41):
Just a jug, like a thermos of
Dr. Thomas Chen (06:43):
Yeah, like a big container. Clovis, at that
time there was no TSA oranything, and Clovis just lugged
it home to Rio De Janeiro. Andso he thought that, I'm a
neurosurgeon, I would like totry on my brain cancer patients.
(07:04):
But at that time, a newprocedure for delivery to the
brain was actually gettingdeveloped in animal models, and
that's called a nasal braindelivery. And the whole concept
of the nasal brain delivery wasthat instead of trying to go
through the blood brain barriersystemically, what you're trying
(07:28):
to do is now deliver, you'rebypassing the blood brain
barrier, and you're deliveringthe drug via the cranial nerves.
And what people found in theanimal models is that there are
two cranial nerves that areparticularly important for nasal
brain delivery. And the firstcranial nerve, I think everybody
(07:50):
knows, is what's called theolfactory nerve. That's the
nerve related to smell. And whatthey found was that in these
patients with the olfactorynerve, that the olfactory nerve
was a very good conduit fordelivery of molecules to the
brain. This is what they foundin animal models.
(08:11):
And also the fifth cranial nerveis the one that's involved with
sensation to the face andability to chew. And so this
sensation of face, the fifthcranial nerve, is also
associated with the nasal braindelivery. So here's the thing.
So Clovis thought that, hey, youknow, so could you bypass that
(08:34):
oral side effect by inhaling itwith the nasal brain delivery?
So the drug, instead of havingto go through your whole body
system to get to the brain,could you just inhale that drug
and take it up to the brain andhave an effect in the brain
cancer?
And so Clovis started treatingpatients. And so what happened
(08:58):
was that he treated about 300patients and these patients had
basically almost no sideeffects. And on top of that,
some of these patients actuallyhad long term survival and their
tumors actually got smaller. Andthis was like, you know, for us,
(09:19):
it's like when we see a braintumor getting smaller on
imaging, that's like a home run.And so Clovis presented his data
to the Brazilian NeurosurgicalSociety.
And he won first place that yearfor that. And because of that,
he won the first place prize wasthat he could go to any lab that
(09:43):
he chose and work there as partof, and he would be granted a
stipend basically. And so hechose to come to USC and work
with me.
Dr. Moira Gunn (09:55):
He chose your lab, that was the prize.
Dr. Thomas Chen (09:58):
He chose my lab, that's right. And when he
came, he was so excited abouthis work. He showed me his MRI
scans and, you know, he reallyhad like patients that had very
large brain tumors, get smalleron further imaging. And I told
(10:19):
Clovis, I said, Well, if this isas good as you say it is, how
come nobody else in the world isdoing this? And I said that,
Well, you know, what we shoulddo is that we should do a
validation study in The UnitedStates and we should, run it
through several academic centershere and see if we can get the
(10:42):
same results you do.
Now, at that time, I wasthinking, okay, so in order for
me to get this drug out to astage where I can do a clinical
trial, where I can get an INDapproved, that all requires
money. Okay? And so I toldClovis that what we need to do
(11:04):
is that we should form a companyand we should, get IP for the
compound And then we shouldapply to the FDA for an IND,
which is Investigational NewDrug, and see if we can, raise
some money from the companyhaving some property and then
(11:26):
run a clinical trial. So thatwas our plan. So then what I did
was that I went to, USC and we,put together a patent.
And the patent was basically forthe use of para alcohol for
treatment of brain cancer. But Itold Clovis that para alcohol is
(11:48):
a commercially availablecompound. And therefore, there
would not be any sort ofintellectual property aside from
the fact that you're now usingit for intranasal delivery. So
what we did was that we went toa local chemistry lab and we
(12:10):
asked the question, can we makethat per alcohol purer than what
it is now? And so what we didwith our local chemistry
company, and they're calledNorac Pharma, is that we asked
the question, could we purifythis?
And could we purify this underGMP or good manufacturing
(12:32):
practice conditions? And youneed to have a drug to be GMP ed
in order to be used in humanpatients. And so, what we were
able to do is that we were ableto add a purification stuff to
this chemical per alcohol, andwe made it into 99.6% pure. And
(12:55):
it was done under GMPconditions. And after we had
done that, we went to the FDAand we wrote a patent for this
purification process.
And we got the patent granted.And then not only the patent
granted, but we also applied fororphan drug status for this
(13:19):
drug, and we also applied forfast track status. But I think
most importantly is that we hada designation of a new chemical
entity with our purificationstep. We then took this set of
information, and then we wrotean IND for a clinical trial. And
(13:42):
at that time, we wrote it forPhase IPhase IIa, and we
submitted it to the FDA, andthey approved it.
And I think that part of thereason we got approved so
rapidly was because the FDArecognized that we're really
dealing with the disease that'slife and death. And so with
(14:03):
that, then what we then did wasthat we got approved and then we
selected some sites to be inthis trial. And the sites that
were involved was the Universityof Southern California, the
Cleveland Clinic, the Universityof Washington up in Seattle, and
University of Wisconsin. Andwith those sites, we then ran a
(14:28):
clinical trial. Now, what I cantell you from our Phase I
testing was that one, thepatients tolerate very well.
They basically had no sideeffects, just like Clovis was
telling me with his patients inBrazil. Two, they didn't have
any of the common toxicitiesthat you would think from
(14:49):
chemotherapy. They didn't theirbone marrow was absolutely
normal. They didn't lose anyhair. They really didn't have
any nausea, vomiting, and noheadaches from inhaling this
product.
And so the patients actuallytolerated very well and did very
well. Now, what we then did wasthat as we went up the dosing,
(15:13):
we found that basically thisheld through even from the
lowest dosage to the highestdosage. Now, along the way, we
also are monitoring thesepatients in terms of how they're
doing clinically. And so eventhough this is a toxicity trial,
(15:33):
we're still getting our MRIscans every two months and
seeing how the tumor is doing.And what we found was that in
some patients, their tumors gotsmaller after inhalation, after
treatment with this therapy.
And in fact, in one patient, thetumor actually disappeared on
(15:54):
MRI scan. And it's what we calla radiographically complete
remission, when the tumor goesaway in MRI scan. And we had
four patients that actuallylived for longer than three
years. Now, so you can say,well, you know, you only had 12
patients. But the thing is thatthe patient population that we
(16:18):
were treating, we were notexpecting these types of results
because the patient populationwe were treating were patients
that had failed conventionaltherapy.
So these were patients that werewhat we call glioblastoma
patients. So they're the worsttype of patients. Their
prognosis on the whole is abouttwelve to fifteen months after
(16:41):
diagnosis. And so thesepatients, undergo conventional
therapy, which is surgery,radiation, and chemotherapy with
a drug called temozolomide.After they fail that treatment,
then they come to our trial.
(17:01):
And so if you ask me like, well,okay, so if you fail
conventional therapy, how longdo you usually live? And the
answer is that most patientshave a survival time of about
five to six months. So we had,four patients that lived longer
than three years. So thequestion is that what was so
(17:23):
unique about their biology thatthey had such a great response
to our drug. And so what we didwas that we went back to their
tumors, we did genomic analysis,and we actually found that they
had something in common.
And that was an IDH1 mutationwithin their tumor cells. And
(17:45):
having that knowledge, I wentback to the FDA and I said, we
had, even though we weresupposed to run just a phase one
study for toxicity, we have fourpatients that did so much better
than expected. And so for ourphase 2A trial, could we just
enroll patients with IDH1mutations who are what we call
(18:09):
recurrent disease and have amalignant glioma. And the FDA
gave us permission to do that.And that resulted in our current
trial, which is a phase 2A, andwe are now almost nearing the
end of our trial.
We have seven more patients toenroll from that 25 patient
(18:33):
cohort. And then we will be donewith the phase 2A. And from
there, we will have a readout interms of how this drug does in
this population of patients, 25patients, in terms of efficacy,
which is what the phase II issupposed to address.
Dr. Moira Gunn (18:52):
What percentage of glioblastoma patients have
this IDH1 mutation? Do we evenknow?
Dr. Thomas Chen (19:00):
Ah, that's a very good question. So, in the
low grade gliomas, in the gradetwos for example, up to fifty
percent of the patient's tumorcould be IDH1 mutations. Now,
when you move up to a gradethree, that number goes down. So
(19:23):
instead of fifty percent beingpositive, it goes down to about
twenty five percent. And thenwhen you go down to a grade
four, which is the glioblastoma,it could be present in three to
five percent.
And so it is correlated with thegrade of the tumor and the
(19:46):
higher grades have a lowerincidence.
Dr. Moira Gunn (19:49):
Okay. So at this point in
Dr. Thomas Chen (19:51):
the
Dr. Moira Gunn (19:51):
story, you have this phase 2a, you're out of
phase one with just the IDH1mutation. So they're in that
stage one, stage two, glioma.And, but what about the rest of
the people?
Dr. Thomas Chen (20:08):
Ah, okay. So, here's the thing is that, well,
first of all, I want to say thatwith the phase 2A, what we want
to establish is that there isefficacy with our treatment.
Now, what we want to do, becausewe're going to have to do a
(20:29):
phase 2B, And the Phase IIb ismost likely going to be about 70
to 80 patients. And so the PhaseIIb would be a larger cohort of
patients. All patients will begetting treated, unlike a phase
three where sometimes there's aplacebo, group.
(20:52):
But with this phase 2B, whatwe're going to do is that we are
going to recruit all comers.Okay? So whether you have an
IDH1 mutation or you don't havean IDH1 mutation, we're going to
be treating them. And then whatwe will be able to do is answer
exactly your question. If youdon't have an IDH1 mutation, how
(21:18):
does that compare when you havethis larger cohort of patients
IDH1 mutations and no IDH1mutations, what is the overall
efficacy and survival time forall patients?
And then how does it comparebetween the two groups? And so
that's coming up. That'ssomething that we are planning
(21:40):
to do for Phase IIb to answerthat question.
Dr. Moira Gunn (21:44):
So what about everybody else?
Dr. Thomas Chen (21:47):
Well, what would happen if we took a drug
that we know has activityagainst brain cancer and we
chemically bind it to the pairalcohol, could we make a new
compound with differentproperties that may be more
effective? And so what we didwas that we took our standard of
(22:11):
care drug, it's calledtemozolomide or TMZ, and we
chemically para alcohol to it.And then we took this new
compound and we put it throughour blood brain barrier program.
Dr. Moira Gunn (22:27):
And by program, you mean a software program, a
computer program.
Dr. Thomas Chen (22:31):
Software program, exactly, exactly. And
what we found was thattemozolomide does cross the
blood brain barrier, but justnot that well. And so we
conjugated to our alcohol, wefound that it crossed the blood
brain barrier much better.
Dr. Moira Gunn (22:49):
Now I want to go back to the first one you did
when you just were trying thosethat phase one, you had four
cohorts of three patients, andyou were increasing the dosage.
And four patients lived, and oneat the time was continuing to
(23:10):
live. Is that patient stillalive today?
Dr. Thomas Chen (23:13):
Actually that patient is still alive today.
And we still, maintain contactwith that patient. And that
patient, actually, you know, Itold you that we get MRI scans
every two months. And now she's,I think, getting MRI scans every
six months now. And continuingto do well.
Dr. Moira Gunn (23:36):
Well, doctor Chen, this has been terrific. I
hope you come back and see usagain.
Dr. Thomas Chen (23:41):
Yeah. I hope so too. Thank you.
Dr. Moira Gunn (23:44):
Doctor Thomas Chen is the director of neuro
oncology at USC and the Founder,CEO, and CSO of NeOnc
Technologies. Three differentclinical trials in brain cancer
are now recruiting. Moreinformation is available on the
web at neonc.com. That's ne0nc,neonc Com.
Popular Podcasts
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.
Dateline NBC
Current and classic episodes, featuring compelling true-crime mysteries, powerful documentaries and in-depth investigations. Follow now to get the latest episodes of Dateline NBC completely free, or subscribe to Dateline Premium for ad-free listening and exclusive bonus content: DatelinePremium.com
On Purpose with Jay Shetty
I’m Jay Shetty host of On Purpose the worlds #1 Mental Health podcast and I’m so grateful you found us. I started this podcast 5 years ago to invite you into conversations and workshops that are designed to help make you happier, healthier and more healed. I believe that when you (yes you) feel seen, heard and understood you’re able to deal with relationship struggles, work challenges and life’s ups and downs with more ease and grace. I interview experts, celebrities, thought leaders and athletes so that we can grow our mindset, build better habits and uncover a side of them we’ve never seen before. New episodes every Monday and Friday. Your support means the world to me and I don’t take it for granted — click the follow button and leave a review to help us spread the love with On Purpose. I can’t wait for you to listen to your first or 500th episode!