This week on BioTech Nation, Dr. Cory Nicholas, CEO of Neurona Therapeutics, returns for part two. With early results now in from Neurona’s first clinical trial, patients with severe epilepsy are seeing dramatic improvements, including seizure reductions of over 90 percent, and even full remission in some cases. This one-time treatment delivers new brain cells that help calm seizure activity without the side effects of traditional medications or the risks of surgery.
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Dr. Moira Gunn (00:11):
This podcast continues our interview with
doctor Corey Nicholas, thefounder and CEO of Neurona
Therapeutics. If you've notlistened to part one, it may be
found at biotechnation.com oryour favorite podcaster.
Recalling that epilepsy is acondition shared by some three
(00:32):
million Americans with fiftymillion or more worldwide,
Neurona has developed and beguntheir very first treatments.
This entails insertingadditional inhibitory cells into
the brain. Their efforts arefocused on the most common type
of epilepsy, temporal lobeepilepsy.
(00:52):
There are now interim results.Okay. So now we are many months,
many months since we firsttalked. Was it two years, I
believe? And you're now in themidst of a phase one two, as we
say, an accelerated study.
(01:14):
And while that's not completed,for a portion of it, there is an
early readout. So let's talkabout what you did in this study
what you see as a result.
Dr. Cory Nicholas (01:28):
So the phase one, trial that's ongoing
originally was in 10 subjects,10 patients. Five received the
low dose of the cell therapythat's called NRTX one thousand
and one, developed by NeuronaTherapeutics. And then a second
(01:53):
five patients received thehigher dose than NRTX-one
thousand and one. Since thosepatients have been treated,
we've enrolled an additional,eight patients into the trial,
So four more at the low dose andfour more at the high dose. You
know, given how well, thingswere going, we we decided to
(02:14):
expand it.
But that was, that happenedlater, and so we don't have the
data yet on that expansiongroup. But we do have some, data
now on the first ten patientsand we shared this recently at
the American Academy ofNeurology Annual Meeting in, San
Diego this past month where wenow have at least one and a half
(02:38):
to two years of follow-up on thefirst five patients to receive
the lower dose of the therapy.And these were people who had
that same form of epilepsy thatwe were talking about earlier.
These are, adult patients whohave drug resistance seizures
coming from one temporal lobeand had failed a number of
(03:03):
medications and decided to trythe cell therapy instead of the
lobectomy or laser ablationsurgeries. And one of the, well,
we always ask the doctors whytheir patients decided to come
into the trial because it's verybrave.
(03:23):
First in human trial don't haveany evidence of precedent of
safety or efficacy. And so thatis truly heroic and altruistic
for these early patients toenroll in a bold effort like
this, not knowing the outcome.But they all say that, one of
the advantages of coming in tothe study, the cell therapy
(03:47):
trial is that you can alwayshave the other surgeries later
if the cell therapy were not towork, that everything stays on
the table essentially. Whereasconversely, you can't do it the
other way around. If you go inand you have a lobectomy to
remove that part of the brain ora laser ablation to destroy that
(04:10):
part of the brain, There is nopart of that brain left to
regenerate.
And so you'll never be able tohave, you know, a cell therapy
or any other option in thefuture. And so I think that, the
mindset for many of the earlypatients, not to put words in
their mouth, but what we'veheard word-of-mouth is that, you
know, this is something thatthey could, you know, as long as
(04:31):
it's safe, they could try, andstill have all of those options
ahead of them. And so they allcame in and they had a single
dose of the cells and, we'vebeen following them and the
trial is still ongoing. So thisis all preliminary, but, we've
seen substantial seizurereduction in four out of those
(04:55):
first five patients. And so, oneof them has become completely
seizure free, for two years.
Two more of them have becomenearly seizure free, meaning
that, just their most severeseizures have been, completely,
eliminated, also out for twoyears. And then a, fourth
(05:20):
patient has had about an 80%reduction from baseline. And so
a very successful outcome. Andthen we've had one patient of
the first five that has notresponded yet. Now this has been
very encouraging, because manyof these folks, as I mentioned,
have the hardest to treatseizures.
(05:42):
Some of them were having, youknow, 20 to 40 seizures a month,
right, despite being onmedications. And so some of them
have spoken out to the press ontheir own accord and have,
commented on how, you know,positively transformative this
has been in helping them to gettheir quality of life back. And
(06:03):
obviously, you know, the trialis still running and time will
tell, But, but it's been reallyphenomenal and encouraging for
the first five patients whooverall have had a, as a group,
a ninety two percent, medianreduction in their baseline
seizure frequency. And that wasat the one year mark. And now
(06:25):
that they're in the second year,as I mentioned, so two of them
are at two years and three ofthem are at a year and a half,
the four that responded in thefirst year have had a durable
response in the second year.
And that's one of the things wedidn't know when we spoke, you
know, many months ago is, youknow, that's great that we're
(06:46):
seeing some early, glimmers ofhope, but will it be durable?
And, so far, you know, fingerscrossed for these folks, it has
been. And, and that's also afterthe, the patients have come off
that immune conditioning,treatment. And it's been very,
very good to see that therehasn't been any sign of relapse
(07:09):
or, you know, loss of responsein the first five patients.
Dr. Moira Gunn (07:18):
What about side effects?
Dr. Cory Nicholas (07:20):
Yeah, so far, we haven't seen any adverse
events related to the celltherapy. And, yeah, there have
been some, mild to moderateeffects due to that immune
conditioning in the firstmonths. Those have generally
been well managed. And, forthese first five individuals
that have now come off of thoseimmune suppressant agents, all
(07:44):
the adverse events that wereattributed, have have, fully
resolved. So there has beennothing, that's persisted,
that's been averse.
And and that's, what we had seenpreclinically as well. And you
never know until you test it inhumans, obviously, but we had a
(08:05):
very, we had good reason tobelieve that, you know, the
cells were gonna be safe. And,this is, you know, through
rigorous testing preclinicallyin a variety of models. And it's
also by design. And so theseneurons, they're not just
indiscriminately pumping outGABA.
(08:27):
It's not like a drug that'spumping out the GABA. The cells,
as I mentioned, become part ofthat network. And so because
they're part of a network, theybecome regulated by the network.
And so we think of them asproviding the GABA on demand.
And so they respond to a seizureby providing a proportional
amount of GABA and they achievethis level of homeostasis that's
(08:51):
really unique as a cell therapy.
It's very much unlike any other,modality where you're giving a
drug and it's just, you know,blasting GABA in the brain and
putting the brain to sleep. Andin all of our preclinical
testing, we never saw any typeof sedation or memory impairment
or fatigue, or any other kind ofadverse effects. So we had a
(09:17):
high degree of confidence, butof course, you know, seeing that
it's been well tolerated in thefirst patients is, very
gratifying.
Dr. Moira Gunn (09:25):
That's really an interesting perspective as well,
because it's like, well, nowyou're gonna be generating this.
We need this. It's like, no. Youonly need it at certain times.
And if any of us say, well, I'venever had a seizure, you don't
know that you didn't haveincipient ones that your GABA
just calmed right down.
Never saw it.
Dr. Cory Nicholas (09:44):
That's exactly right. And so, in fact,
one of the patients of the firstfive who's had a really nice
response actually came in for anEEG. And the EEG measures these
lower level of spikes in thispart of the brain, and they're
almost like the monomer buildingblocks of a seizure. And so even
(10:08):
though this patient was havingonly, I say only tongue in cheek
because this patient was having,I believe, 40 seizures a month,
which are, you know, behavioralseizures. They were having a
thousand epileptic type ofspikes per hour.
(10:29):
So to your point, Moira, thisepileptic activity is oftentimes
subclinical, and people don'tknow that that's happening
underneath and driving thegradual buildup of this activity
that eventually, you know, runsaway like a runaway train and
(10:50):
causes a seizure.
Dr. Moira Gunn (10:51):
Now there is not just a tremendous unmet need
here. I know the FDA has givenyou expedited review designation
and you've begun to design aphase three clinical trial. What
do you expect to see in thisphase three trial, knowing that
your phase one, two is ongoing?
Dr. Cory Nicholas (11:11):
Right. So we, based on this early data,
submitted an application to theFDA for what's called an RMAT
designation, which stands forRegenerative Medicine Advanced
Therapy. And that's, similar toa breakthrough designation, but
for regenerative therapies. And,to be eligible for this, you
(11:35):
have to have some clinical datathat suggests that this could
be, you know, potentially,efficacious and, you know,
filling an important need as aregenerative medicine for
serious, illness. And, you know,given that we were seeing
encouraging signs of seizuresuppression and safety, and I
(11:58):
did mention also that, we've notseen any permanent cognitive
deficits.
We've not seen memory loss or,you know, any type of, impact on
on, you know, quality of lifeor, you know, other other type
(12:21):
of neuropsychological, impacts.In fact, you know, we we've seen
a couple of the patients withsignificantly improved scores on
these very, sensitiveneuropsychological tests. And so
with this body of evidence, the,FDA granted us the RMAT
designation in the middle oflast year. And then this
(12:44):
provides additional meetingswith the agency to discuss how
to best advance the program in asafe manner. And and so with
this, these conversations haveled to an alignment with the
agency on the design of a singlephase three study.
Dr. Moira Gunn (13:06):
I'm speaking with doctor Cory Nicholos, the
cofounder and CEO VeronaTherapeutics,
Dr. Cory Nicholas (13:13):
a former member of the faculty and
postdoc in the Department
Dr. Moira Gunn (13:17):
of Neurology at UC San Francisco. His research
work, in part, evaluated thetherapeutic potential of
interneuron cell therapy inneurological disease. I'm Moira
Gunn. You're listening to TechNation. When might you be
(13:46):
recruiting for that?
Dr. Cory Nicholas (13:48):
And so the, plan is to start enrolling in
the second half of the year,this year.
Dr. Moira Gunn (13:54):
So this year, 2025.
Dr. Cory Nicholas (13:56):
That's right.
Dr. Moira Gunn (13:57):
Fall of twenty twenty five. Watch this space, I
hear. I hear. Yes. Which isextremely fast, especially on
ongoing phase onetwo.
It's like they see real promisehere, obviously.
Dr. Cory Nicholas (14:09):
Right. Well, phase onetwo primary endpoint is
at one year. And so the firstfive patients at the lower dose
have surpassed the one yearendpoint in the phase one, two.
As I mentioned, they're now offalmost near the end of the
second year. And then we had asecond dose that was a higher
(14:29):
dose in another five patientsthat we reported interim data on
at the AAN meeting, which isalso showing promise and we're
seeing a similar reduction,although that cohort hasn't yet
made it all the way to the oneyear mark.
And so we're seeing, you know,encouraging effects at both dose
levels. Preclinically, didn'tsee a difference in the dose
(14:52):
levels with respect to safety orefficacy. And so we think that
they're behaving in much thesame way. But in other words, by
the middle of the year, we willhave completed the one year
endpoint on both of the dosingcohorts and we'll be ready to
pick a dose to go into the phasethree. And the phase three is
designed as a randomized doubleblind controlled trial of the
(15:16):
cell therapy versus a shamcontrol group.
And the sham control group inthis case, is, sham procedure.
And so, patients that come intothe study will be randomized and
meaning that they won't knowwhich arm they're gonna be put
into. And two thirds of themwill receive the cell therapy
(15:39):
and one third will not. And theywill essentially be anesthetized
and nothing will enter thebrain. So there's nothing
injected, there's nothingtouching the brain.
It's essentially a shamprocedure, and they'll wake up
not knowing if they had thecells or not. And then, we will
follow these patients for aperiod of time until they reach
(16:00):
the primary endpoint, at whichpoint they'll become unblinded
and they'll find out which groupthey were in. And if they were
found to be in the sham group,they will then have the
opportunity to receive the celltherapy at that point.
Dr. Moira Gunn (16:16):
Now when I first interviewed you, we were just
wishing and hoping we'd see someresults here. And not only, has
this all been moving along,Dorona has another phase one,
phase two on a on a differentaspect, if you will, of this, as
(16:37):
well as a number of pipelinesand some new science. Some of
that new science, I'm not evensure what it's about. But why
don't you give us a shot? Tellus about your your other
pipelines and and clinicaltrials, and tell us about your
new science.
Dr. Cory Nicholas (16:50):
Right, well, we're very excited about
NRTX-one thousand and one forthe treatment of focal epilepsy
beyond just the one temporallobe that we're currently
treating. And so we have asecond phase one, two trial that
is active, actively enrollingin, people that have the same
disease, MTLE or mesial temporalepilepsy, on both sides of the
(17:15):
brain. So both essentially hastwo seizure foci. And then in
this population, in a singleprocedure, we'll be, injecting
the cell therapy into both ofthe temporal lobes
simultaneously. And in this way,you know, attempting to quench
the seizures coming from bothtemporal lobes of the brain.
And this is a population thathas, if you can believe it, even
(17:38):
higher unmet need because peoplethat have two seizure foci in
both temporal lobes are noteligible to have lobectomy
procedures by and large becauseif you destroy or remove both
temporal lobes, you becomeseverely amnestic, right,
because the temporal lobe is thepart of the brain that controls
(17:59):
memory formation. And so thispopulation of patients truly has
no other option. And, we're veryhopeful that the same results
can be extended to this group.And, this trial is actively
enrolling. It'll be in 10adults.
And so you can go on ourwebsite,
neuronotherapeutics.com, to findout more information about the
(18:21):
trials and the eligibilitycriteria. We have another study
that's also active. That's acontinuation of the first, the
unilateral trial that I justwent through. And this is in a
slightly different population ofpatients that has epilepsy
coming from the part of thebrain that is not damaged on the
(18:44):
MRI. It's a bit of a nuance, butthese individuals have their
seizure foci identifiedexclusively by EEG, which in
many people, they cannot seewhere the seizures are coming
from on the MRI.
And so it's very important to beable to triangulate the seizure
focus by EEG and to show that wecould administer the cells into
(19:05):
this population identified inthis way, to hopefully have the
same outcome and broaden theapplicability. And so trials are
ongoing. We have studies runningat approximately 30 centers
across The United States. Theseare the accredited comprehensive
(19:25):
centers that I mentionedearlier. And so, you know,
encourage folks to to go and ifthey or, loved ones are affected
with drug refractory seizures,to go to a level, three or four
center period to have a workupto evaluate options.
And, of course, if you'reinterested in the trial, could
talk to your physician aboutwhether or not you would be a
(19:48):
good candidate for the celltherapy investigation if that's
of interest. Beyond temporallobe epilepsy, we do have very
much, interested in testingwhether or not this same therapy
can be effective in seizurescoming from other lobes of the
brain beyond the temporal lobe.And there are many adults and
(20:12):
children that have, differentailments in the cerebral cortex.
Many, have what's called focalcortical dysplasias where a part
of the brain doesn't developnormally and can cause seizures
that are difficult to manage.And so many of these are in
(20:32):
areas of the brain that can't beremoved, what are called
eloquent areas of the brain.
And so we would like to test, inthe future whether the cell
therapy approach can be safe andeffective in those folks. And
then beyond epilepsy, we and bythe way, there are other
(20:53):
epilepsies of interest. I shouldmention that there are many
epilepsies in other parts of thebrain that start in one or more
places, we're not sure why theystart and there's no clear
fingerprint to to see wherethey're coming from. We're
interested in those. There arealso others that are due to, to
secondary to traumas, like atraumatic brain injury or a
(21:16):
stroke or a tumor.
And so these are sort of wherewe're headed with the, with this
approach. And then beyondepilepsy, we are interested in,
Alzheimer's disease, Parkinson'sdisease, neuropathic pain, and
potentially neuropsychiatricdisorders like schizophrenia and
(21:37):
PTSD. And that's a big, basketof things. But the thing that's
common about them all is thatthey share this hyperactive
pathophysiology, thishyperactive circuitry of too
much electrical activity comingthrough that circuit. And so at
its core is the same fundamentalof putting these inhibitory
(22:01):
cells to quiet that part of thebrain, repair that part of the
brain in a homeostatic, youknow, manner.
Dr. Moira Gunn (22:09):
So you're after it. You're you're looking for
too much excitement. You're verycalm, Doctor. Nicholas. I like
this.
Now I have to say that you'vebeen at this a long time. It
must feel great to finally seesome some just real results
(22:29):
here.
Dr. Cory Nicholas (22:30):
We've been working on this for a very long
time. This goes back to the latenineteen nineties, in the labs
of my cofounders at theUniversity of California, San
Francisco, where many of thesediscoveries were first made. And
it has been a long journey, andit's very gratifying to see it
(22:50):
move truly from bench tobedside. And, you know, to see
the early results are fantastic.And also, you know, it always
has to come with the level ofscientific rigor and, the
caveats that it's still early,and so we need to keep testing
it.
And and we think that the phasethree study that will be
designed in anywhere between, 30and, 90 patients, and we're
(23:15):
still fine tuning the samplesize based on the maturing
dataset from the phase one,trial, which we aim to lock down
by the middle of the year andthen in advance of starting that
phase three trial in, the secondhalf of this year. But we think
that, you know, this next trialwill be, being that it's a
(23:36):
double blind controlled study,will be of the highest rigor to
conclusively determine whetheror not the approach is working.
And, you know, we hope to thenat that point, take it beyond
The United States and to look,you know, at Europe, for
example, and, Asia and and startto advance this for for everyone
(23:56):
that may be looking for analternative.
Dr. Moira Gunn (23:58):
Well, doctor Nicholas, thank you so much for
coming in, and I hope you comeback and see us again.
Dr. Cory Nicholas (24:04):
Well, thank you so much, Moya, for having me
back on. It's a pleasure. And Ijust want to thank the amazing
team at Neurona for theirdedication in developing this
and continuing to advance thistherapy and program for epilepsy
and other disorders of thenervous system. I want to thank
our clinical collaborators. As Imentioned, this is a several
(24:25):
hundred person effort now with,30 medical centers around The
United States and growing.
I want to sincerely thank thepatients and their families who
are part of this program and byparticipating in this, advancing
our understanding, andhopefully, making this available
for more patients in the future.And I I lastly, I want to thank
(24:48):
the California Institute forRegenerative Medicine, which has
helped to fund a lot of thiswork. And so we're very lucky,
here in the state of California.
Dr. Moira Gunn (24:59):
Doctor. Corey Nicholas is the co founder and
CEO of Neurona Therapeutics.More information is available on
the web at neuronatx.com. That'sneurona, n e u r 0 n a, neurona
t x Com. Each of the clinicaltrials for which Neurona is
(25:22):
actively recruiting and whichDoctor.
Nicholas has just described arepresented in detail on the
Neurona Therapeutics website. Itidentifies participating
centers, direct contactinformation, eligibility
parameters including preciseinclusion and exclusion criteria
on becoming a study participant,timelines, the measurements
(25:46):
being examined, theparticipation level required,
and how travel expenses, if any,will be handled. This
information can be found underthe tab Clinical Trials at
Neuronas website, neuronatx.com.For information about Level
three and Level four epilepsycenters near you, the National
(26:09):
Association of Epilepsy Centerslinks 300 member centers in 44
states. The website is naeceepilepsy Org.
Wide ranging information aboutepilepsy, as well as
understanding and living withepilepsy, is available from the
(26:29):
Epilepsy Foundation. Theirwebsite is epilepsy.com.
This podcast continues our interview with
doctor Corey Nicholas, thefounder and CEO of Neurona
Therapeutics. If you've notlistened to part one, it may be
found at biotechnation.com oryour favorite podcaster.
Recalling that epilepsy is acondition shared by some three
(00:32):
million Americans with fiftymillion or more worldwide,
Neurona has developed and beguntheir very first treatments.
This entails insertingadditional inhibitory cells into
the brain. Their efforts arefocused on the most common type
of epilepsy, temporal lobeepilepsy.
(00:52):
There are now interim results.Okay. So now we are many months,
many months since we firsttalked. Was it two years, I
believe? And you're now in themidst of a phase one two, as we
say, an accelerated study.
(01:14):
And while that's not completed,for a portion of it, there is an
early readout. So let's talkabout what you did in this study
what you see as a result.
Dr. Cory Nicholas (01:28):
So the phase one, trial that's ongoing
originally was in 10 subjects,10 patients. Five received the
low dose of the cell therapythat's called NRTX one thousand
and one, developed by NeuronaTherapeutics. And then a second
(01:53):
five patients received thehigher dose than NRTX-one
thousand and one. Since thosepatients have been treated,
we've enrolled an additional,eight patients into the trial,
So four more at the low dose andfour more at the high dose. You
know, given how well, thingswere going, we we decided to
(02:14):
expand it.
But that was, that happenedlater, and so we don't have the
data yet on that expansiongroup. But we do have some, data
now on the first ten patientsand we shared this recently at
the American Academy ofNeurology Annual Meeting in, San
Diego this past month where wenow have at least one and a half
(02:38):
to two years of follow-up on thefirst five patients to receive
the lower dose of the therapy.And these were people who had
that same form of epilepsy thatwe were talking about earlier.
These are, adult patients whohave drug resistance seizures
coming from one temporal lobeand had failed a number of
(03:03):
medications and decided to trythe cell therapy instead of the
lobectomy or laser ablationsurgeries. And one of the, well,
we always ask the doctors whytheir patients decided to come
into the trial because it's verybrave.
(03:23):
First in human trial don't haveany evidence of precedent of
safety or efficacy. And so thatis truly heroic and altruistic
for these early patients toenroll in a bold effort like
this, not knowing the outcome.But they all say that, one of
the advantages of coming in tothe study, the cell therapy
(03:47):
trial is that you can alwayshave the other surgeries later
if the cell therapy were not towork, that everything stays on
the table essentially. Whereasconversely, you can't do it the
other way around. If you go inand you have a lobectomy to
remove that part of the brain ora laser ablation to destroy that
(04:10):
part of the brain, There is nopart of that brain left to
regenerate.
And so you'll never be able tohave, you know, a cell therapy
or any other option in thefuture. And so I think that, the
mindset for many of the earlypatients, not to put words in
their mouth, but what we'veheard word-of-mouth is that, you
know, this is something thatthey could, you know, as long as
(04:31):
it's safe, they could try, andstill have all of those options
ahead of them. And so they allcame in and they had a single
dose of the cells and, we'vebeen following them and the
trial is still ongoing. So thisis all preliminary, but, we've
seen substantial seizurereduction in four out of those
(04:55):
first five patients. And so, oneof them has become completely
seizure free, for two years.
Two more of them have becomenearly seizure free, meaning
that, just their most severeseizures have been, completely,
eliminated, also out for twoyears. And then a, fourth
(05:20):
patient has had about an 80%reduction from baseline. And so
a very successful outcome. Andthen we've had one patient of
the first five that has notresponded yet. Now this has been
very encouraging, because manyof these folks, as I mentioned,
have the hardest to treatseizures.
(05:42):
Some of them were having, youknow, 20 to 40 seizures a month,
right, despite being onmedications. And so some of them
have spoken out to the press ontheir own accord and have,
commented on how, you know,positively transformative this
has been in helping them to gettheir quality of life back. And
(06:03):
obviously, you know, the trialis still running and time will
tell, But, but it's been reallyphenomenal and encouraging for
the first five patients whooverall have had a, as a group,
a ninety two percent, medianreduction in their baseline
seizure frequency. And that wasat the one year mark. And now
(06:25):
that they're in the second year,as I mentioned, so two of them
are at two years and three ofthem are at a year and a half,
the four that responded in thefirst year have had a durable
response in the second year.
And that's one of the things wedidn't know when we spoke, you
know, many months ago is, youknow, that's great that we're
(06:46):
seeing some early, glimmers ofhope, but will it be durable?
And, so far, you know, fingerscrossed for these folks, it has
been. And, and that's also afterthe, the patients have come off
that immune conditioning,treatment. And it's been very,
very good to see that therehasn't been any sign of relapse
(07:09):
or, you know, loss of responsein the first five patients.
Dr. Moira Gunn (07:18):
What about side effects?
Dr. Cory Nicholas (07:20):
Yeah, so far, we haven't seen any adverse
events related to the celltherapy. And, yeah, there have
been some, mild to moderateeffects due to that immune
conditioning in the firstmonths. Those have generally
been well managed. And, forthese first five individuals
that have now come off of thoseimmune suppressant agents, all
(07:44):
the adverse events that wereattributed, have have, fully
resolved. So there has beennothing, that's persisted,
that's been averse.
And and that's, what we had seenpreclinically as well. And you
never know until you test it inhumans, obviously, but we had a
(08:05):
very, we had good reason tobelieve that, you know, the
cells were gonna be safe. And,this is, you know, through
rigorous testing preclinicallyin a variety of models. And it's
also by design. And so theseneurons, they're not just
indiscriminately pumping outGABA.
(08:27):
It's not like a drug that'spumping out the GABA. The cells,
as I mentioned, become part ofthat network. And so because
they're part of a network, theybecome regulated by the network.
And so we think of them asproviding the GABA on demand.
And so they respond to a seizureby providing a proportional
amount of GABA and they achievethis level of homeostasis that's
(08:51):
really unique as a cell therapy.
It's very much unlike any other,modality where you're giving a
drug and it's just, you know,blasting GABA in the brain and
putting the brain to sleep. Andin all of our preclinical
testing, we never saw any typeof sedation or memory impairment
or fatigue, or any other kind ofadverse effects. So we had a
(09:17):
high degree of confidence, butof course, you know, seeing that
it's been well tolerated in thefirst patients is, very
gratifying.
Dr. Moira Gunn (09:25):
That's really an interesting perspective as well,
because it's like, well, nowyou're gonna be generating this.
We need this. It's like, no. Youonly need it at certain times.
And if any of us say, well, I'venever had a seizure, you don't
know that you didn't haveincipient ones that your GABA
just calmed right down.
Never saw it.
Dr. Cory Nicholas (09:44):
That's exactly right. And so, in fact,
one of the patients of the firstfive who's had a really nice
response actually came in for anEEG. And the EEG measures these
lower level of spikes in thispart of the brain, and they're
almost like the monomer buildingblocks of a seizure. And so even
(10:08):
though this patient was havingonly, I say only tongue in cheek
because this patient was having,I believe, 40 seizures a month,
which are, you know, behavioralseizures. They were having a
thousand epileptic type ofspikes per hour.
(10:29):
So to your point, Moira, thisepileptic activity is oftentimes
subclinical, and people don'tknow that that's happening
underneath and driving thegradual buildup of this activity
that eventually, you know, runsaway like a runaway train and
(10:50):
causes a seizure.
Dr. Moira Gunn (10:51):
Now there is not just a tremendous unmet need
here. I know the FDA has givenyou expedited review designation
and you've begun to design aphase three clinical trial. What
do you expect to see in thisphase three trial, knowing that
your phase one, two is ongoing?
Dr. Cory Nicholas (11:11):
Right. So we, based on this early data,
submitted an application to theFDA for what's called an RMAT
designation, which stands forRegenerative Medicine Advanced
Therapy. And that's, similar toa breakthrough designation, but
for regenerative therapies. And,to be eligible for this, you
(11:35):
have to have some clinical datathat suggests that this could
be, you know, potentially,efficacious and, you know,
filling an important need as aregenerative medicine for
serious, illness. And, you know,given that we were seeing
encouraging signs of seizuresuppression and safety, and I
(11:58):
did mention also that, we've notseen any permanent cognitive
deficits.
We've not seen memory loss or,you know, any type of, impact on
on, you know, quality of lifeor, you know, other other type
(12:21):
of neuropsychological, impacts.In fact, you know, we we've seen
a couple of the patients withsignificantly improved scores on
these very, sensitiveneuropsychological tests. And so
with this body of evidence, the,FDA granted us the RMAT
designation in the middle oflast year. And then this
(12:44):
provides additional meetingswith the agency to discuss how
to best advance the program in asafe manner. And and so with
this, these conversations haveled to an alignment with the
agency on the design of a singlephase three study.
Dr. Moira Gunn (13:06):
I'm speaking with doctor Cory Nicholos, the
cofounder and CEO VeronaTherapeutics,
Dr. Cory Nicholas (13:13):
a former member of the faculty and
postdoc in the Department
Dr. Moira Gunn (13:17):
of Neurology at UC San Francisco. His research
work, in part, evaluated thetherapeutic potential of
interneuron cell therapy inneurological disease. I'm Moira
Gunn. You're listening to TechNation. When might you be
(13:46):
recruiting for that?
Dr. Cory Nicholas (13:48):
And so the, plan is to start enrolling in
the second half of the year,this year.
Dr. Moira Gunn (13:54):
So this year, 2025.
Dr. Cory Nicholas (13:56):
That's right.
Dr. Moira Gunn (13:57):
Fall of twenty twenty five. Watch this space, I
hear. I hear. Yes. Which isextremely fast, especially on
ongoing phase onetwo.
It's like they see real promisehere, obviously.
Dr. Cory Nicholas (14:09):
Right. Well, phase onetwo primary endpoint is
at one year. And so the firstfive patients at the lower dose
have surpassed the one yearendpoint in the phase one, two.
As I mentioned, they're now offalmost near the end of the
second year. And then we had asecond dose that was a higher
(14:29):
dose in another five patientsthat we reported interim data on
at the AAN meeting, which isalso showing promise and we're
seeing a similar reduction,although that cohort hasn't yet
made it all the way to the oneyear mark.
And so we're seeing, you know,encouraging effects at both dose
levels. Preclinically, didn'tsee a difference in the dose
(14:52):
levels with respect to safety orefficacy. And so we think that
they're behaving in much thesame way. But in other words, by
the middle of the year, we willhave completed the one year
endpoint on both of the dosingcohorts and we'll be ready to
pick a dose to go into the phasethree. And the phase three is
designed as a randomized doubleblind controlled trial of the
(15:16):
cell therapy versus a shamcontrol group.
And the sham control group inthis case, is, sham procedure.
And so, patients that come intothe study will be randomized and
meaning that they won't knowwhich arm they're gonna be put
into. And two thirds of themwill receive the cell therapy
(15:39):
and one third will not. And theywill essentially be anesthetized
and nothing will enter thebrain. So there's nothing
injected, there's nothingtouching the brain.
It's essentially a shamprocedure, and they'll wake up
not knowing if they had thecells or not. And then, we will
follow these patients for aperiod of time until they reach
(16:00):
the primary endpoint, at whichpoint they'll become unblinded
and they'll find out which groupthey were in. And if they were
found to be in the sham group,they will then have the
opportunity to receive the celltherapy at that point.
Dr. Moira Gunn (16:16):
Now when I first interviewed you, we were just
wishing and hoping we'd see someresults here. And not only, has
this all been moving along,Dorona has another phase one,
phase two on a on a differentaspect, if you will, of this, as
(16:37):
well as a number of pipelinesand some new science. Some of
that new science, I'm not evensure what it's about. But why
don't you give us a shot? Tellus about your your other
pipelines and and clinicaltrials, and tell us about your
new science.
Dr. Cory Nicholas (16:50):
Right, well, we're very excited about
NRTX-one thousand and one forthe treatment of focal epilepsy
beyond just the one temporallobe that we're currently
treating. And so we have asecond phase one, two trial that
is active, actively enrollingin, people that have the same
disease, MTLE or mesial temporalepilepsy, on both sides of the
(17:15):
brain. So both essentially hastwo seizure foci. And then in
this population, in a singleprocedure, we'll be, injecting
the cell therapy into both ofthe temporal lobes
simultaneously. And in this way,you know, attempting to quench
the seizures coming from bothtemporal lobes of the brain.
And this is a population thathas, if you can believe it, even
(17:38):
higher unmet need because peoplethat have two seizure foci in
both temporal lobes are noteligible to have lobectomy
procedures by and large becauseif you destroy or remove both
temporal lobes, you becomeseverely amnestic, right,
because the temporal lobe is thepart of the brain that controls
(17:59):
memory formation. And so thispopulation of patients truly has
no other option. And, we're veryhopeful that the same results
can be extended to this group.And, this trial is actively
enrolling. It'll be in 10adults.
And so you can go on ourwebsite,
neuronotherapeutics.com, to findout more information about the
(18:21):
trials and the eligibilitycriteria. We have another study
that's also active. That's acontinuation of the first, the
unilateral trial that I justwent through. And this is in a
slightly different population ofpatients that has epilepsy
coming from the part of thebrain that is not damaged on the
(18:44):
MRI. It's a bit of a nuance, butthese individuals have their
seizure foci identifiedexclusively by EEG, which in
many people, they cannot seewhere the seizures are coming
from on the MRI.
And so it's very important to beable to triangulate the seizure
focus by EEG and to show that wecould administer the cells into
(19:05):
this population identified inthis way, to hopefully have the
same outcome and broaden theapplicability. And so trials are
ongoing. We have studies runningat approximately 30 centers
across The United States. Theseare the accredited comprehensive
(19:25):
centers that I mentionedearlier. And so, you know,
encourage folks to to go and ifthey or, loved ones are affected
with drug refractory seizures,to go to a level, three or four
center period to have a workupto evaluate options.
And, of course, if you'reinterested in the trial, could
talk to your physician aboutwhether or not you would be a
(19:48):
good candidate for the celltherapy investigation if that's
of interest. Beyond temporallobe epilepsy, we do have very
much, interested in testingwhether or not this same therapy
can be effective in seizurescoming from other lobes of the
brain beyond the temporal lobe.And there are many adults and
(20:12):
children that have, differentailments in the cerebral cortex.
Many, have what's called focalcortical dysplasias where a part
of the brain doesn't developnormally and can cause seizures
that are difficult to manage.And so many of these are in
(20:32):
areas of the brain that can't beremoved, what are called
eloquent areas of the brain.
And so we would like to test, inthe future whether the cell
therapy approach can be safe andeffective in those folks. And
then beyond epilepsy, we and bythe way, there are other
(20:53):
epilepsies of interest. I shouldmention that there are many
epilepsies in other parts of thebrain that start in one or more
places, we're not sure why theystart and there's no clear
fingerprint to to see wherethey're coming from. We're
interested in those. There arealso others that are due to, to
secondary to traumas, like atraumatic brain injury or a
(21:16):
stroke or a tumor.
And so these are sort of wherewe're headed with the, with this
approach. And then beyondepilepsy, we are interested in,
Alzheimer's disease, Parkinson'sdisease, neuropathic pain, and
potentially neuropsychiatricdisorders like schizophrenia and
(21:37):
PTSD. And that's a big, basketof things. But the thing that's
common about them all is thatthey share this hyperactive
pathophysiology, thishyperactive circuitry of too
much electrical activity comingthrough that circuit. And so at
its core is the same fundamentalof putting these inhibitory
(22:01):
cells to quiet that part of thebrain, repair that part of the
brain in a homeostatic, youknow, manner.
Dr. Moira Gunn (22:09):
So you're after it. You're you're looking for
too much excitement. You're verycalm, Doctor. Nicholas. I like
this.
Now I have to say that you'vebeen at this a long time. It
must feel great to finally seesome some just real results
(22:29):
here.
Dr. Cory Nicholas (22:30):
We've been working on this for a very long
time. This goes back to the latenineteen nineties, in the labs
of my cofounders at theUniversity of California, San
Francisco, where many of thesediscoveries were first made. And
it has been a long journey, andit's very gratifying to see it
(22:50):
move truly from bench tobedside. And, you know, to see
the early results are fantastic.And also, you know, it always
has to come with the level ofscientific rigor and, the
caveats that it's still early,and so we need to keep testing
it.
And and we think that the phasethree study that will be
designed in anywhere between, 30and, 90 patients, and we're
(23:15):
still fine tuning the samplesize based on the maturing
dataset from the phase one,trial, which we aim to lock down
by the middle of the year andthen in advance of starting that
phase three trial in, the secondhalf of this year. But we think
that, you know, this next trialwill be, being that it's a
(23:36):
double blind controlled study,will be of the highest rigor to
conclusively determine whetheror not the approach is working.
And, you know, we hope to thenat that point, take it beyond
The United States and to look,you know, at Europe, for
example, and, Asia and and startto advance this for for everyone
(23:56):
that may be looking for analternative.
Dr. Moira Gunn (23:58):
Well, doctor Nicholas, thank you so much for
coming in, and I hope you comeback and see us again.
Dr. Cory Nicholas (24:04):
Well, thank you so much, Moya, for having me
back on. It's a pleasure. And Ijust want to thank the amazing
team at Neurona for theirdedication in developing this
and continuing to advance thistherapy and program for epilepsy
and other disorders of thenervous system. I want to thank
our clinical collaborators. As Imentioned, this is a several
(24:25):
hundred person effort now with,30 medical centers around The
United States and growing.
I want to sincerely thank thepatients and their families who
are part of this program and byparticipating in this, advancing
our understanding, andhopefully, making this available
for more patients in the future.And I I lastly, I want to thank
(24:48):
the California Institute forRegenerative Medicine, which has
helped to fund a lot of thiswork. And so we're very lucky,
here in the state of California.
Dr. Moira Gunn (24:59):
Doctor. Corey Nicholas is the co founder and
CEO of Neurona Therapeutics.More information is available on
the web at neuronatx.com. That'sneurona, n e u r 0 n a, neurona
t x Com. Each of the clinicaltrials for which Neurona is
(25:22):
actively recruiting and whichDoctor.
Nicholas has just described arepresented in detail on the
Neurona Therapeutics website. Itidentifies participating
centers, direct contactinformation, eligibility
parameters including preciseinclusion and exclusion criteria
on becoming a study participant,timelines, the measurements
(25:46):
being examined, theparticipation level required,
and how travel expenses, if any,will be handled. This
information can be found underthe tab Clinical Trials at
Neuronas website, neuronatx.com.For information about Level
three and Level four epilepsycenters near you, the National
(26:09):
Association of Epilepsy Centerslinks 300 member centers in 44
states. The website is naeceepilepsy Org.
Wide ranging information aboutepilepsy, as well as
understanding and living withepilepsy, is available from the
(26:29):
Epilepsy Foundation. Theirwebsite is epilepsy.com.
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