July 9, 2025 • 16 mins
Dr. John Scarlett, President and CEO of Geron Corporation talks about their drug Imetelstat for myelodysplastic syndrome (MDS). MDS patients often require frequent blood transfusions, impacting their quality of life. Imetelstat, a telomerase inhibitor, aims to reduce transfusion dependence by targeting cancer cells in the bone marrow. Phase three trials showed promising results, with 40% of patients experiencing at least an 8-week transfusion-free interval.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Moira Gunn (00:11):
Can you imagine having to get a blood
transfusion every few weeks justto continue living? That's what
life is like for the 20 to 30000new patients each year and
numerous more who suffer from acondition called MDS. Doctor
John Scarlett is president andCEO of Geron Corporation. Doctor
(00:34):
Scarlett, welcome to theprogram.
Dr. John Scarlett (00:37):
Thanks so much, Moira. I really appreciate
it.
Dr. Moira Gunn (00:39):
Now before we start, I do wanna tell everyone
that Geron has a drug which hasmade it successfully through the
phase three clinical trials.We're always saying, how are you
doing? Where are you in thephase three clinical trials? And
has what we call a PDUFA date,coming up with the FDA, where
the FDA hopefully is gonna saythumbs up. It usually says
(01:01):
thumbs up, but let's make surewe get there, and that's when we
can commercialize and go tomarket.
But before we do that, let's laysome groundwork. If there's one
thing we all need and we we knowwe need it, it's for our bodies
to produce blood cells, goodhealthy blood cells in the
quantities we need. Now we'retalking about, MDS today. What
(01:26):
is it? How is it treated?
Dr. John Scarlett (01:29):
MDS, which stands for myelodysplastic
syndrome, is a bone marrowcancer that results in
inadequate production of bloodcells. And in the form of MDS
that we're studying, thosecancer cells take over the bone
marrow and do not produce thenormal amounts of red blood
(01:53):
cells, which is the oxygencarrying portion of blood that's
so important for our dailylives. And so patients with MDS,
the version we study, theybecome anemic and eventually
become transfusion dependent. Sothe goal is, above all, to get
(02:16):
them off of transfusions if atall possible.
Dr. Moira Gunn (02:20):
How often do they have to get a transfusion?
Dr. John Scarlett (02:22):
So it's a progressive disease, and what
might start out as sort of awatch and wait, eventually,
these patients sometimes becomemildly transfusion dependent,
meaning they may only need 1 or2 units of red blood cells every
couple of months. Buteventually, they become heavily
(02:43):
transfusion dependent. Andthat's actually a really
terrible thing, from a couple ofperspectives. 1, they're
tethered. 2, they have to be inan infusion center to get those
transfusions very frequently,often as frequently as every
other week.
(03:03):
That entails a lot of logistics,a lot of driving, waiting around
for blood to be cross typed andmatched. Sometimes the blood has
to be brought in from anothercenter because they didn't have
the right blood for them. And sothey become really dependent on,
on, becoming dependent on thesetransfusions also means they
(03:26):
become really hobbled. Theirquality of their life, their
daily living is really hobbledby that. And so they may take
upwards of 10 units of red cellsevery couple of months.
And that in and of itself alsocauses dangers. Red blood cell
transfusions, cause depositionof iron in major, organs, and
(03:51):
that can cause failure of thoseorgans. And so there's there's
lots of things that transfusionsdo that you would really like to
make people transfusion free orreduce the burden of transfusion
as much as possible.
Dr. Moira Gunn (04:05):
So here's where Geron comes in. This is where
you're working. What is yourdrug doing specifically? Because
I know in the overall, you wannaget them off those transfusions.
But what is it doingspecifically about this
condition?
Dr. John Scarlett (04:22):
So our drug is what is called the telomerase
inhibitor. And, you know, allcells ordinarily have a normal
life cycle. They get born. Theydo whatever they do as cells,
and then they die in a prettyorderly fashion. And they die
after, you know, proliferating afew rounds, and then they then
(04:46):
they senescence and die.
But cancer cells in general, andthese MDS cells in particular in
our case, actually have, anenzyme in the bone marrow that
is upregulated calledtelomerase, which causes those
(05:08):
cells to continue toproliferate. And as long as that
enzyme is present andupregulated, they're going to
become, much longer lived and,as I say, proliferate at very
high rates. So a telomeraseinhibitor is intended to take
away that that enzyme's action,and then the cells become more
(05:31):
like normal cells, andeventually, the proliferation
lowers. They apoptosamine die.
Dr. Moira Gunn (05:37):
Now if I understand what you're saying is
that if I had this condition,these cells would, like, not die
filling up my bone marrow.They're not producing healthy
blood cells. So over time, Ihave fewer and fewer of those.
And what your drug is doing isit's going in finding those
(05:58):
cells and saying, no, I'm afraidyou're gonna have to die, which
makes room for your healthyblood cells.
Dr. John Scarlett (06:04):
That's exactly right, Mara. Just as
you, alluded in patients treatedwith a telomerase inhibitor,
ideally they become far lessdependent on or not dependent
on, transfusions to addresstheir anemia, and, lots of other
(06:26):
good things happen to them inthat regard. So that's a a key
goal, of treatment.
Dr. Moira Gunn (06:32):
Now as I said earlier, you have not only
gotten into phase 3, you'vecompleted phase 3. And that
meant phase 1 went well, phase 2went well, and now you really
have a good body of knowledge.Tell us about this phase 3
trial. What did you do? Who wasin it?
(06:52):
How long did it last?
Dr. John Scarlett (06:54):
Right. So this was a study that was done
in many, many centers around theworld, including United States,
North American general, also inthe far east and certainly in,
in Europe. And we took patientswho had a version of MDS called
(07:16):
lower risk MDS, just as we'vedescribed. And we randomized
them to receive eitherImetelstat or placebo. Of course
they could continue to receivetransfusions if needed.
And so for example, the majorityof placebo patients continue to
receive transfusions. And then,percentage of patients, that no
(07:41):
longer needed transfusions,really was the main outcome of
that study, outcome measure ofthat study. And in our case, 40%
of the patients had at least an8 week transfusion free
interval, in the Imetelstattreated or the drugs treated arm
(08:03):
as opposed to the placebotreated arm. What's really
impressive though is that thosepatients, actually went on to
have, on average about a year ofnot requiring transfusions. And
that's really substantially,better than you could do with
any other drugs that have beenon the market prior to this.
Dr. Moira Gunn (08:24):
So that's what leads you to successful phase 3.
That's great. Now a lot ofpeople think, well, that means
just go out and startmanufacturing and distributing
it to, medical centerseverywhere and and doctors. But
the truth is is there's a spacebetween successful phase 3 and
this PDUFA date. PDUFA are theletters p d u f a.
(08:49):
They come from the US governmentact, Prescription Drug User Fee
Act. And it has to do withthat's the date that the FDA
will have absolutely done awhole lot of stuff in reviewing
exactly what went on. So tellus, as a company, you get these
great results and you get fromhere to the PDUFA date. What do
(09:11):
you do then?
Dr. John Scarlett (09:12):
Well, the first thing you do is you make
an application to the governmentthrough the FDA to be allowed to
market the product. And we callthat a new drug application or
NDA. That, generally is filedabout a year before you would
expect to be be approved. And inthat application, which covers
(09:36):
literally all aspects of yourdrug, all aspects of the
disease, You make all thearguments why the data, strongly
support the idea that theefficacy of the drug is more
than adequate and actually thatthe benefit risk of the drug is
(09:58):
strongly in favour of treatmentwith the drug. And that's the
fundamental lens through whichthe FDA looks.
But of course there are many,many, different, angles that
are, looked at, in both theefficacy and the safety side of
the product. Once you're throughthat review, if you will, then
(10:18):
there's other things that you dowith the FDA, which include,
agreeing on the professionalinstructions for use of the
drug, which we call variouslythe package insert, which people
would be very familiar with. Youget a package insert. Most of
the time, you get a prescriptiondrug. It's usually a very large
(10:40):
piece of paper that's folded upvery tiny and stuck on the, on
the, on the, on the drugscontainer.
You also there there's, therealmost every aspect of the sale
of a product in the UnitedStates, via this, via the
approval of an NDA is covered inthe whole review and approval
(11:02):
process down to what theadvertising can say and how you
can say it.
Dr. Moira Gunn (11:07):
Now I forgot to ask you how many people were in
that last phase 3?
Dr. John Scarlett (11:13):
Right. There were a 180 people in that last
phase 3. And, as I said, theywere in a a large, a large
number of, of centers around theworld.
Dr. Moira Gunn (11:23):
Lot of people for a lot of months. A lot of
months. Well, it's like, guesswhat? Your PDUFA date is coming
right up. June 16, 2024.
You've turned in, I guess, justabout everything to the FDA so
far, and now you're waiting.
Dr. John Scarlett (11:40):
Yeah. There's, some back and forth
still, but, what I would say isthat right now, the company is
really focused on being ready tostart to sell the product if
approved. That would most likelycome around the time of the
PDUFA date, as you've said.There's a huge amount of
(12:03):
activity that's focused onsupplying the commercial needs
of the market once you do haveapproval. And you have to kind
of anticipate that, right,because you don't wanna get an
approval and then not be able togo out and provide the drug to
the market, in appropriate wayfor months.
(12:23):
And so we've hired sales reps,we've got a whole commercial
team working on the correctmessaging and the, access to the
healthcare system, which in thiscountry is very complex and
requires a lot of people to sortof navigate all the different
ways that we end up getting drugto patients and we end up
(12:44):
getting information to theirhealth care providers and and
hematologists in this case, sothat they know, how best to use
the drug and and so forth.
Dr. Moira Gunn (12:55):
Well, it's it's kind of amazing in one sense.
It's like, well, we just talkedabout this for a few minutes.
The PDUFA date's coming up in 4weeks, at the time of this
interview. And this has been a30 year journey. You just didn't
get here now.
I mean, tell us, just just sortof quickly, you know, what
what's the what are the bones,the bare bones of that 30 year
(13:18):
journey, and what does it feellike now?
Dr. John Scarlett (13:21):
So I will get to what it feels like now, which
I can summarize very simply assaying it feels great. But the
30 year journey is what youoften see behind the scenes in
highly innovative products.Because you really start out
with a hypothesis that a certainmechanism, a certain enzyme to
(13:43):
be, targeted, whatever, is isimportant and and can be
targeted, but you don't evenhave a drug to target it. And so
the first thing you really workon usually is getting a drug,
and that can take quite a numberof years as you go through the
process, you know, the chemistryand the biology of, of
(14:07):
manufacturing and making a drugthat is, is appropriate to
interact with the target, inthis case, the telomerase
target. And then the second thenyou, once you've done that, you
have to do a lot of preclinical,studies to establish appropriate
(14:27):
doses and safety and efficacy,and then you go into the clinic.
And as you know, Mara, there'susually phase 1, which is first
time in man. That's oftenlooking for evidence of activity
in different areas that youthink might be valuable. Then
once you've settled on that,then you have phase 2, which
explores dose and the and theway in which you, give the
(14:51):
product to patients andestablishes the background for
proving that your, ideas abouthow to use use the drug can be
proved in what we call usually adouble blind and randomized
controlled study, which is whatis the long name for a phase 3
study, which, establishes thethe strength of the data, that
(15:16):
regulators can look at and thatthey can hopefully believe in
that allows you then to beapproved.
Dr. Moira Gunn (15:22):
30 years to be an overnight success. I think
that
Dr. John Scarlett (15:25):
That's a good way to put it.
Dr. Moira Gunn (15:26):
How to phrase that? Doctor John Scarlett is
the president and CEO of GeronCorporation. More information is
available at geron.com. That'sger0n, geron.com.
Can you imagine having to get a blood
transfusion every few weeks justto continue living? That's what
life is like for the 20 to 30000new patients each year and
numerous more who suffer from acondition called MDS. Doctor
John Scarlett is president andCEO of Geron Corporation. Doctor
(00:34):
Scarlett, welcome to theprogram.
Dr. John Scarlett (00:37):
Thanks so much, Moira. I really appreciate
it.
Dr. Moira Gunn (00:39):
Now before we start, I do wanna tell everyone
that Geron has a drug which hasmade it successfully through the
phase three clinical trials.We're always saying, how are you
doing? Where are you in thephase three clinical trials? And
has what we call a PDUFA date,coming up with the FDA, where
the FDA hopefully is gonna saythumbs up. It usually says
(01:01):
thumbs up, but let's make surewe get there, and that's when we
can commercialize and go tomarket.
But before we do that, let's laysome groundwork. If there's one
thing we all need and we we knowwe need it, it's for our bodies
to produce blood cells, goodhealthy blood cells in the
quantities we need. Now we'retalking about, MDS today. What
(01:26):
is it? How is it treated?
Dr. John Scarlett (01:29):
MDS, which stands for myelodysplastic
syndrome, is a bone marrowcancer that results in
inadequate production of bloodcells. And in the form of MDS
that we're studying, thosecancer cells take over the bone
marrow and do not produce thenormal amounts of red blood
(01:53):
cells, which is the oxygencarrying portion of blood that's
so important for our dailylives. And so patients with MDS,
the version we study, theybecome anemic and eventually
become transfusion dependent. Sothe goal is, above all, to get
(02:16):
them off of transfusions if atall possible.
Dr. Moira Gunn (02:20):
How often do they have to get a transfusion?
Dr. John Scarlett (02:22):
So it's a progressive disease, and what
might start out as sort of awatch and wait, eventually,
these patients sometimes becomemildly transfusion dependent,
meaning they may only need 1 or2 units of red blood cells every
couple of months. Buteventually, they become heavily
(02:43):
transfusion dependent. Andthat's actually a really
terrible thing, from a couple ofperspectives. 1, they're
tethered. 2, they have to be inan infusion center to get those
transfusions very frequently,often as frequently as every
other week.
(03:03):
That entails a lot of logistics,a lot of driving, waiting around
for blood to be cross typed andmatched. Sometimes the blood has
to be brought in from anothercenter because they didn't have
the right blood for them. And sothey become really dependent on,
on, becoming dependent on thesetransfusions also means they
(03:26):
become really hobbled. Theirquality of their life, their
daily living is really hobbledby that. And so they may take
upwards of 10 units of red cellsevery couple of months.
And that in and of itself alsocauses dangers. Red blood cell
transfusions, cause depositionof iron in major, organs, and
(03:51):
that can cause failure of thoseorgans. And so there's there's
lots of things that transfusionsdo that you would really like to
make people transfusion free orreduce the burden of transfusion
as much as possible.
Dr. Moira Gunn (04:05):
So here's where Geron comes in. This is where
you're working. What is yourdrug doing specifically? Because
I know in the overall, you wannaget them off those transfusions.
But what is it doingspecifically about this
condition?
Dr. John Scarlett (04:22):
So our drug is what is called the telomerase
inhibitor. And, you know, allcells ordinarily have a normal
life cycle. They get born. Theydo whatever they do as cells,
and then they die in a prettyorderly fashion. And they die
after, you know, proliferating afew rounds, and then they then
(04:46):
they senescence and die.
But cancer cells in general, andthese MDS cells in particular in
our case, actually have, anenzyme in the bone marrow that
is upregulated calledtelomerase, which causes those
(05:08):
cells to continue toproliferate. And as long as that
enzyme is present andupregulated, they're going to
become, much longer lived and,as I say, proliferate at very
high rates. So a telomeraseinhibitor is intended to take
away that that enzyme's action,and then the cells become more
(05:31):
like normal cells, andeventually, the proliferation
lowers. They apoptosamine die.
Dr. Moira Gunn (05:37):
Now if I understand what you're saying is
that if I had this condition,these cells would, like, not die
filling up my bone marrow.They're not producing healthy
blood cells. So over time, Ihave fewer and fewer of those.
And what your drug is doing isit's going in finding those
(05:58):
cells and saying, no, I'm afraidyou're gonna have to die, which
makes room for your healthyblood cells.
Dr. John Scarlett (06:04):
That's exactly right, Mara. Just as
you, alluded in patients treatedwith a telomerase inhibitor,
ideally they become far lessdependent on or not dependent
on, transfusions to addresstheir anemia, and, lots of other
(06:26):
good things happen to them inthat regard. So that's a a key
goal, of treatment.
Dr. Moira Gunn (06:32):
Now as I said earlier, you have not only
gotten into phase 3, you'vecompleted phase 3. And that
meant phase 1 went well, phase 2went well, and now you really
have a good body of knowledge.Tell us about this phase 3
trial. What did you do? Who wasin it?
(06:52):
How long did it last?
Dr. John Scarlett (06:54):
Right. So this was a study that was done
in many, many centers around theworld, including United States,
North American general, also inthe far east and certainly in,
in Europe. And we took patientswho had a version of MDS called
(07:16):
lower risk MDS, just as we'vedescribed. And we randomized
them to receive eitherImetelstat or placebo. Of course
they could continue to receivetransfusions if needed.
And so for example, the majorityof placebo patients continue to
receive transfusions. And then,percentage of patients, that no
(07:41):
longer needed transfusions,really was the main outcome of
that study, outcome measure ofthat study. And in our case, 40%
of the patients had at least an8 week transfusion free
interval, in the Imetelstattreated or the drugs treated arm
(08:03):
as opposed to the placebotreated arm. What's really
impressive though is that thosepatients, actually went on to
have, on average about a year ofnot requiring transfusions. And
that's really substantially,better than you could do with
any other drugs that have beenon the market prior to this.
Dr. Moira Gunn (08:24):
So that's what leads you to successful phase 3.
That's great. Now a lot ofpeople think, well, that means
just go out and startmanufacturing and distributing
it to, medical centerseverywhere and and doctors. But
the truth is is there's a spacebetween successful phase 3 and
this PDUFA date. PDUFA are theletters p d u f a.
(08:49):
They come from the US governmentact, Prescription Drug User Fee
Act. And it has to do withthat's the date that the FDA
will have absolutely done awhole lot of stuff in reviewing
exactly what went on. So tellus, as a company, you get these
great results and you get fromhere to the PDUFA date. What do
(09:11):
you do then?
Dr. John Scarlett (09:12):
Well, the first thing you do is you make
an application to the governmentthrough the FDA to be allowed to
market the product. And we callthat a new drug application or
NDA. That, generally is filedabout a year before you would
expect to be be approved. And inthat application, which covers
(09:36):
literally all aspects of yourdrug, all aspects of the
disease, You make all thearguments why the data, strongly
support the idea that theefficacy of the drug is more
than adequate and actually thatthe benefit risk of the drug is
(09:58):
strongly in favour of treatmentwith the drug. And that's the
fundamental lens through whichthe FDA looks.
But of course there are many,many, different, angles that
are, looked at, in both theefficacy and the safety side of
the product. Once you're throughthat review, if you will, then
(10:18):
there's other things that you dowith the FDA, which include,
agreeing on the professionalinstructions for use of the
drug, which we call variouslythe package insert, which people
would be very familiar with. Youget a package insert. Most of
the time, you get a prescriptiondrug. It's usually a very large
(10:40):
piece of paper that's folded upvery tiny and stuck on the, on
the, on the, on the drugscontainer.
You also there there's, therealmost every aspect of the sale
of a product in the UnitedStates, via this, via the
approval of an NDA is covered inthe whole review and approval
(11:02):
process down to what theadvertising can say and how you
can say it.
Dr. Moira Gunn (11:07):
Now I forgot to ask you how many people were in
that last phase 3?
Dr. John Scarlett (11:13):
Right. There were a 180 people in that last
phase 3. And, as I said, theywere in a a large, a large
number of, of centers around theworld.
Dr. Moira Gunn (11:23):
Lot of people for a lot of months. A lot of
months. Well, it's like, guesswhat? Your PDUFA date is coming
right up. June 16, 2024.
You've turned in, I guess, justabout everything to the FDA so
far, and now you're waiting.
Dr. John Scarlett (11:40):
Yeah. There's, some back and forth
still, but, what I would say isthat right now, the company is
really focused on being ready tostart to sell the product if
approved. That would most likelycome around the time of the
PDUFA date, as you've said.There's a huge amount of
(12:03):
activity that's focused onsupplying the commercial needs
of the market once you do haveapproval. And you have to kind
of anticipate that, right,because you don't wanna get an
approval and then not be able togo out and provide the drug to
the market, in appropriate wayfor months.
(12:23):
And so we've hired sales reps,we've got a whole commercial
team working on the correctmessaging and the, access to the
healthcare system, which in thiscountry is very complex and
requires a lot of people to sortof navigate all the different
ways that we end up getting drugto patients and we end up
(12:44):
getting information to theirhealth care providers and and
hematologists in this case, sothat they know, how best to use
the drug and and so forth.
Dr. Moira Gunn (12:55):
Well, it's it's kind of amazing in one sense.
It's like, well, we just talkedabout this for a few minutes.
The PDUFA date's coming up in 4weeks, at the time of this
interview. And this has been a30 year journey. You just didn't
get here now.
I mean, tell us, just just sortof quickly, you know, what
what's the what are the bones,the bare bones of that 30 year
(13:18):
journey, and what does it feellike now?
Dr. John Scarlett (13:21):
So I will get to what it feels like now, which
I can summarize very simply assaying it feels great. But the
30 year journey is what youoften see behind the scenes in
highly innovative products.Because you really start out
with a hypothesis that a certainmechanism, a certain enzyme to
(13:43):
be, targeted, whatever, is isimportant and and can be
targeted, but you don't evenhave a drug to target it. And so
the first thing you really workon usually is getting a drug,
and that can take quite a numberof years as you go through the
process, you know, the chemistryand the biology of, of
(14:07):
manufacturing and making a drugthat is, is appropriate to
interact with the target, inthis case, the telomerase
target. And then the second thenyou, once you've done that, you
have to do a lot of preclinical,studies to establish appropriate
(14:27):
doses and safety and efficacy,and then you go into the clinic.
And as you know, Mara, there'susually phase 1, which is first
time in man. That's oftenlooking for evidence of activity
in different areas that youthink might be valuable. Then
once you've settled on that,then you have phase 2, which
explores dose and the and theway in which you, give the
(14:51):
product to patients andestablishes the background for
proving that your, ideas abouthow to use use the drug can be
proved in what we call usually adouble blind and randomized
controlled study, which is whatis the long name for a phase 3
study, which, establishes thethe strength of the data, that
(15:16):
regulators can look at and thatthey can hopefully believe in
that allows you then to beapproved.
Dr. Moira Gunn (15:22):
30 years to be an overnight success. I think
that
Dr. John Scarlett (15:25):
That's a good way to put it.
Dr. Moira Gunn (15:26):
How to phrase that? Doctor John Scarlett is
the president and CEO of GeronCorporation. More information is
available at geron.com. That'sger0n, geron.com.
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