Dr. Peter DeMuth, Chief Scientific Officer of Elicio Therapeutics, discusses the revolutionary approach of detecting cancer at its earliest stages through circulating tumor DNA (ctDNA) tests. Highlighting their innovative treatment method, which aims to train the body's immune cells to recognize and destroy cancer cells, the episode explores the potential transition from treatment to vaccine, offering hope for more effective and durable solutions.
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Dr. Moira Gunn (00:11):
There are few things more anxiety producing
than having to go in and get ascan to see if your cancer may
have returned. And thankfully,scans do pick up tiny tumors.
But what if we could seecharacteristics of that cancer
much earlier while they weresimply individual cancer cells?
(00:32):
And what if that ability mightlead directly to a treatment or
even a vaccine, recognizing andeliminating those cells should
they appear in the future?Today, we learn how Elicio
Therapeutics is working to dojust that.
Doctor Peter DeMuth is its chiefscientific officer. Doctor
(00:52):
Demuth, welcome to the program.
Dr. Peter DeMuth (00:54):
Thank you. It's great to be here, Moira.
Dr. Moira Gunn (00:57):
Now I've been thinking about a place to start
and I'm hoping this is the rightplace. You know, we we've all
heard about DNA, but you use theterm ctDNA. What is ctDNA?
Dr. Peter DeMuth (01:10):
Yeah. That's a great place to start. So ctDNA
stands for circulating tumorDNA, and this is DNA that is
released by tumor cells thatmight be present in the body.
And some of this DNA, when it'sreleased, is able to make its
way into the blood. And then itcan be detected with a
specialized test that analyzes apatient's blood.
(01:32):
And these tests are reallyinteresting because they're
based upon a DNA signaturethat's found in the tumor. It's
specific for the tumor almostlike a fingerprint. So these
tests are designed to work bydetecting that DNA signature of
the tumor in the blood so thatif we see this fingerprint in
the blood test, it tells us thata tumor is present somewhere in
(01:56):
the body.
Dr. Moira Gunn (01:57):
Now is this new technology? Have we been using
it for some time? Where are wewith this?
Dr. Peter DeMuth (02:04):
It's it's relatively new. We're definitely
seeing progress, and these typesare types of tests are being
designed and perfected overtime. So we're looking to
improve the way that we candetect cancer using these ctDNA
tests, and the other reallyinteresting opportunity is to
use them to, inform thetreatments that we design for
(02:25):
patients. So taking a big stepback right now, most of the
time, cancer patients arediagnosed using medical imaging
techniques. And this can give usimportant information about a
tumor, can show it us where itis or how advanced it is, and it
can even be used once patientsare on treatment so that we can
(02:46):
monitor the tumor, and it cantell us whether the cancer is
responding to a particulartherapy.
Is it getting bigger? Is itgetting smaller? Is it
completely gone? So imaging isreally useful, but these ctDNA
tests could be used in many ofthe same ways to detect a tumor,
to learn something about thetumor, to understand if a
(03:07):
treatment is working, but thectDNA tests have some really
important advantages. So thismight help us to treat cancer
more effectively.
One of the big advantages isthat because ctDNA tests use
blood, they can be moreconvenient than going for
repeated medical imaging. Butalso, and this is the big one,
ctDNA tests can be extremelysensitive. So for example,
(03:30):
medical imaging might only beable to detect a tumor that is
about a centimeter in size, butsince ctDNA tests are based on
DNA, they might be able todetect the presence of a much
smaller tumor that would notordinarily show up on a medical
scan. And the reason this isimportant is because with
cancer, treating early when atumor is small and more
(03:53):
manageable gives us the bestchance to be successful. So,
overall, it's really exciting tosee these tests being used more
often and in different ways, andI think that could really help
improve patient care.
Dr. Moira Gunn (04:05):
Now do we have to know the tumor profile, the
tumor DNA for a particularperson to compare it to see it
in the blood?
Dr. Peter DeMuth (04:16):
Yeah. Many of these, tests are built upon, an
analysis of a tumor that's doneearly on when a patient is first
diagnosed, and then thatinformation is used to develop
the fingerprint that Imentioned, the signature of the
tumor, and that signature iswhat is analyzed in the blood.
So some of those tests are builton that concept, but others use
(04:38):
more basic information that isshared and common across many
different tumors in manydifferent patients.
Dr. Moira Gunn (04:44):
So let's say I have cancer surgery. If all the
cancer is removed, then weshould not see any ctDNA in my
blood. Right?
Dr. Peter DeMuth (04:54):
That's exactly right. So if a tumor is truly
completely removed by surgery orit's destroyed by a therapy
that's effective, there would beno tumor cells left in the body
to produce that ctDNA. And inthat case, the ctDNA test would
be negative. It would show nodetectable levels of ctDNA or
(05:15):
presence of that tumor signaturein the blood.
Dr. Moira Gunn (05:18):
And going on from here, if there are cells
that are remaining, will theycontinue to grow and we
eventually see their ctDNA?
Dr. Peter DeMuth (05:27):
Absolutely. And I can give you a really good
example of this. So one areawhere ctDNA tests are being used
is to evaluate patients aftersurgery. So, of course, the goal
of surgery is to completelyremove the cancer, but,
realistically, that can be verydifficult to do. So ctDNA can
give us a very sensitive tool todetermine whether there's tumor
(05:51):
remaining after surgery.
So if ctDNA is present, we referto that as molecular relapse. So
this is because we can see thesignature of the tumor on a
molecular level, And this isoften at a point where standard
medical imaging may not be ableto detect that tumor at all. So
(06:11):
by using this approach, we'veseen that patients with
molecular relapse after surgery,they're more likely to develop
that visible tumor on theirscans, and this happens much
more quickly compared topatients that don't have
detectable ctDNA after surgery.So having this information gives
us a really good opportunity totreat these patients earlier
(06:34):
when the overall amount of tumoris small and the goal, is to see
that ctDNA level decrease or,best case scenario, go away
completely. And if we're able toachieve that, the expectation is
that we could prevent recurrenceof the tumor and patients might
have longer and healthier lives.
Dr. Moira Gunn (06:54):
Now let's get to what Eliseo is doing. What are
you doing?
Dr. Peter DeMuth (06:57):
Yeah. So till now we've talked about how we
can determine the DNA signatureof a tumor as part of that ctDNA
test. But the tumor signature isimportant in other ways. For
example, it could give us cluesabout what parts of the tumor we
can target with treatment. Forexample, what parts of the tumor
differentiate it from normalhealthy cells, and these
(07:19):
differences could be really goodtargets for a potential
treatment.
So our goal at Alesio is to usethat information, that signature
of the tumor, to train theimmune cells of the body.
Essentially, we want the body'sown immune cells to use that
tumor signature to identifycancer cells specifically and
then to destroy them. And it'sprobably helpful to pause here
(07:41):
and say something quickly aboutthe immune system. When we talk
about the immune system, what wereally mean is the millions of
immune cells that are present inour bodies, and there are
different types of immune cells.Each cell type has a function
and a job, and overall, thesecells work together to protect
us from infectious disease,bacteria, from viruses, but they
(08:03):
can also protect us from our owncells if they become mutated and
have the potential to becomecancer.
So one of the jobs of the immuneresponse is to detect these
mutated cells and, ideally, tokill them before they're able to
become cancer. And oneparticular type of immune cell I
wanna mention is important forthis. Some people may know these
(08:25):
as t cells. But if not, what youneed to know about these cells
is that they patrol throughoutthe body. Part of their job is
to recognize the mutations thatdevelop in cancerous cells.
In other words, they coulddetect if a cell has that
signature or that fingerprintthat's associated with cancer.
And with the right training,they can search out and destroy
(08:46):
those cells. So to bring it allback, the idea at Alysio is to
design treatments that can trainthese immune cells so they can
first recognize that cancersignature and have the ability
to kill those cancer cellswherever they find them in the
body.
Dr. Moira Gunn (09:03):
So you're smartening up these t cells,
these immune cells, and they'retrans they're all over your body
looking. Looking looking lookinglooking.
Dr. Peter DeMuth (09:10):
That's exactly right.
Dr. Moira Gunn (09:11):
I feel like my body is so smart. Make your body
smarter. It could be your model.It could be your model.
Dr. Peter DeMuth (09:17):
We often call the lymph nodes the schoolhouse
of the immune system for thatexact reason. We're taking these
immune cells to school.
Dr. Moira Gunn (09:25):
Now you just mentioned your lymph nodes. What
do what do they have to do withwith these these immune cells,
these t cells you're smartening
Dr. Peter DeMuth (09:35):
up? That's a great point, Moira, and and I'll
get to that. Let me first startby talking to you about these
signatures a little bit more.One of the main signatures that
we're looking for in the cancersthat we're trying to treat is
called KRAS. KRAS is a mutationpresent in many different
tumors.
It's part of that tumorsignature. In fact, it's present
in about 20 5% of all humansolid cancers, including
(09:59):
pancreatic and colorectal andlung cancers. And in total,
these mutations affect cancersthat are present in 100 of
thousands of patients in the USevery year. So if we could
design a treatment that wouldtake those immune cells to
school, train them up so thatthey recognize that mutant form
of KRAS, these cells would thenbe able to go out and destroy
(10:22):
those cancer cells throughoutthe body. For for example, they
could be useful to to eradicatecancer cells that could be left
over after surgery and preventthose cells from growing and
causing recurrence of the tumor.
So let's get to the lymph nodes,as you mentioned. So training
(10:42):
these immune cells is a bigchallenge, and the lymph nodes,
we believe, are the solution tothat challenge. So the average
person might not think aboutlymph nodes very much, but
they're very important for theimmune response. These are the
primary sites in our body, wherethe immune cells come together,
where they exchange informationwith with each other. They serve
(11:04):
as training centers for theimmune response.
So in essence, where the immunecells coordinate all the
activities that they need toperform to defend the body. So
the strategy at Alysio is to getthese types of treatments to the
lymph nodes, and that has been abig challenge. Typically, these
types of treatments, afterthey're dosed, they're diverted
(11:24):
away from the lymph nodes, andso they might miss their chance
to train those immune cells. Butwhat we're doing at Alysio is
developing a new class, a newtype of treatment that are
targeted directly to the lymphnodes where we can train those
immune cells more effectively.And this is something that has
taken a lot of work.
And the strategy that we'vedeveloped is based on albumin,
(11:48):
this very common protein in thebody, which has a very useful
property in that it travels veryspecifically precisely into the
lymph nodes. So we're lookingwith our approach to take
advantage of this, and we can dothat by engineering our
treatments to attach to albuminafter they're injected, and this
allows us to directly targetthose treatments to immune cells
(12:11):
in the lymph nodes. So the ideahere is that once in the lymph
nodes, those treatments caneducate immune cells so they
recognize the tumor, and thosecells are able to patrol
throughout the body, searchwherever they find cancer cells,
they're programmed to kill them,and do that specifically while
leaving normal healthy cellsuntouched. And if we're able to
(12:33):
do that, we've got a really goodshot at at treating cancer
effectively.
Dr. Moira Gunn (12:38):
So you're taking albumin, which we've all heard
of, you know, is very common inthe body, and you're engineering
that signature onto the albumin,then the albumin goes into the
lymph node and says, hey, thisis what you gotta The back end
says, this is what you gottalook for. That's what's making
(13:00):
the t cell smart?
Dr. Peter DeMuth (13:02):
Yeah. That's exactly right. This is this is
all about delivery. We haveinformation that we wanna get to
the immune cells, and albumin isable to get that information
directly into the place wherethe immune cells are are where
they are and where they can usethat information to develop the
right responses to treat cancer.
Dr. Moira Gunn (13:19):
So you're also making smart albumin?
Dr. Peter DeMuth (13:22):
Well, albumin is already smart. You're just
taking advantage of the thingsit knows how to do really well.
Dr. Moira Gunn (13:28):
Alright. Alright. We're there. Now, I
know you're in phase 2 forpancreatic cancer. Every phase 2
started with a phase 1.
Let's take us back there so weknow what you did in phase 1.
Who you looked at, the humansyou looked at, what you tested,
and what you learned.
Dr. Peter DeMuth (13:47):
Yeah. So I'd love to do that. The phase one
trial was looking at 25 patientswith pancreatic and colorectal
cancer, a group that is insignificant need of new
therapies. These patients hadalready been through the
standard treatments. So in thiscase, that's chemotherapy and
surgery to remove their tumor.
And after that, they'reevaluated using medical imaging
(14:12):
to understand the state of theircancer. We're essentially
looking to see if we can findany tumor remaining. And for
patients coming on to the trial,the answer there was no. The
scans didn't show anything. Wecan't see a tumor, but, this is
a big but, when we look withthat more sensitive ctDNA blood
test, we see the tumor.
We're able to see that thosetumor cells are still present,
(14:34):
and, unfortunately, this meansthat the cancer is likely to
return and at that point toprogress really quickly. So with
this information, what we askedwas, can we treat those patients
to eliminate the remaining tumorcells that we detected with the
ctDNA test? And by doing that,could we potentially prevent the
(14:54):
cancer from returning? So that'sexactly what we tried to do, and
we saw some really interestingthings. So the the first thing
we saw was the immune response.
We, in this case, wanted tocount, essentially, to count the
number of tumor killing immunecells that were present in these
patients before and after thetreatment. And what we saw was
(15:14):
that after treatment, the numberof immune cells was increased in
the vast majority of thepatients on that trial. So,
obviously, this suggests thatthe treatment is doing a good
job of training up those immunecells. After that, we wanted to
see whether patients hadreductions in the level of their
ctDNA, and we saw that that wasthe case in many patients. In
(15:36):
fact, almost a quarter of thepatients completely cleared
their CT DNA, which means itwent to 0 undetectable.
And so that is suggestive thatthe residual tumor cells that
were present after surgery werebeing killed. And what's really
exciting, the last thing wewanted to do was see whether the
strength of the immune response,the number of immune cells, was
(15:58):
in any way connected to how wellpatients did overall. And so
what we did is we looked at thetime that patients would take to
relapse or to pass away fromtheir disease and measured that
against the strength of the tcell, the immune cell response.
And what we saw was that therewas an 86% decrease in the risk
(16:19):
of recurrence of death orrelapse in patients that
developed the strongest, thebest immune cells to our
treatment. So this is obviouslyreally exciting, and it shows
that the treatment is bothgenerating those immune cells,
training them up, and that ifpatients get those types of
responses in their immunesystem, they may be able to
(16:41):
delay or prevent the return oftheir cancer.
So, obviously, now our job is toconfirm that in the phase 2
study.
Dr. Moira Gunn (16:48):
And as happens in phase 2, you look at what
happened in phase 1, and youdon't just continue it. You say,
okay. Maybe we'll target this ormaybe we'll change this. And so
while you will, at some point,work on colorectal, you decided
in phase 2 just to focus on thepancreatic cancer. Now tell us
what that is and how that'sdifferent.
Dr. Peter DeMuth (17:10):
Yeah. That that's exactly right. So the
phase one look at both. We haveto make a choice in phase 2, and
we chose to look at pancreaticcancer. And there's some good
reasons for that.
We know that pancreatic cancersare often mutated with this KRAS
mutation, so they have the exactsignature that the treatment was
designed to address. So manypatients with this type of
(17:31):
cancer could benefit. We alsoknow that pancreatic cancer is
one of the deadliest cancers. Ithas a 5 year survival of less
than 20%, so patients are in invery great need of new
therapies. So in this trial, thephase 2, we're again looking at
pancreatic cancer patients,again looking at patients that
(17:52):
have completed their standard,treatments, either chemotherapy
or surgery, both most likely.
And, again, the standardapproach here is observation. So
doctors are just waiting.They're monitoring. They're
looking for that tumor toreturn, and they know that it
will. So in the trial, insteadof just waiting, instead of just
(18:13):
watching, we're gonna look tosee if this experimental
treatment can delay or evencompletely prevent the return of
the tumor.
And, again, because this is aphase 2 study, we'll have the
opportunity to compare theoutcomes in those patients, the
ones that get the treatment, tothose who receive the standard
observation. And this will allowus to measure how well the
(18:36):
treatment works.
Dr. Moira Gunn (18:37):
And how many people are in that study?
Dr. Peter DeMuth (18:41):
Approximately a 135. So patients will be split
to either get treatment or toget observation, and then we'll
be able to follow them again tolook for the amount of time that
it takes for patients to have arecurrence of their tumor or to
pass away, and that will give usa chance to observe the benefits
that we could potentially seewith this treatment.
Dr. Moira Gunn (19:02):
And if they're not getting Eliseo's treatment,
they're still getting all theother treatments that they were
Dr. Peter DeMuth (19:08):
That's exactly right. Be.
Dr. Moira Gunn (19:10):
Designed to be given. Yeah.
Dr. Peter DeMuth (19:11):
Exactly.
Dr. Moira Gunn (19:11):
So no one is without treatment in this?
Dr. Peter DeMuth (19:14):
That's exactly right. Yes.
Dr. Moira Gunn (19:15):
That's great. Now you keep saying if they got
the treatment. Is this a onetimedelivery?
Dr. Peter DeMuth (19:21):
So the treatment is, multiple doses. So
we give 4 doses in the 1st monthand 2 additional doses in the
2nd month. And so this is theinitiation, the first the first
training session for the immuneresponse, if you will. And then
we give those immune cells alittle bit of a break, and then
we come back in and we trainthem again. We give them another
(19:42):
4 doses.
So, essentially, another lesson,another, another session to
learn the the lessons that we'retrying to teach them.
Dr. Moira Gunn (19:50):
So, you know, this really is science. We have
to figure out how much is toomuch, how much is too little,
how much is enough. There'sthere are questions here.
Dr. Peter DeMuth (20:00):
Absolutely. Yes. There there are tons of
things we're still learning. Oneof the really interesting
questions here is how manyimmune cells we need to be
effective? Also, what sort ofqualities or functions those
cells need to have in order tobe effective killers and finders
of tumor cells in the body.
And I think the biggest thingthat we're most interested to
(20:21):
study, and that's the main goalof the phase 2, is, again,
whether this type of treatmentcould prevent the cancer from
turning from returning, and ifso, how long that that
protection might last.
Dr. Moira Gunn (20:33):
So this starts out as a treatment because
you're treating cancer that ispresent. And if it prevents it
in the future, it becomes avaccine.
Dr. Peter DeMuth (20:43):
That's exactly right. So this can prevent the
return of cancer in the future,but it certainly starts out in
your body as a treatment. Andthis is one of the most amazing
things about the immune system,essentially that it has a
memory, that it can remember thepast dangers that it's
experienced before. And this isreally important because it
(21:04):
means that the immune cells thatremember can react more quickly
to protect you from threats thatyou might see again in the
future. So, certainly, whilethis treatment is designed to
address cancer that's presentnow, the immune system can form
that long lasting memory, and itmight be able to recognize
future cancer cells and thenprevent them from returning and
(21:24):
causing the disease to progress.
So it's certainly a reallyexciting opportunity to treat
patients, but also to give thempotentially really long lasting
and durable freedom fromdisease.
Dr. Moira Gunn (21:37):
So any future cancer with a KRAS mutation,
hopefully, it would say youmight be a completely different
cancer, but we have you. Butthere are other mutations and
other unique mutations.
Dr. Peter DeMuth (21:50):
Yeah. Absolutely. There are many
different mutations. Cancers arevery diverse. So this is the
type of therapy that could beused to target those other
signatures of the tumor, andthat's kind of the exciting part
looking into the future.
We're learning how to trainthese immune cells. We're
teaching them how to see tumorcells behind them and destroy
(22:13):
them. We've worked really hard,and we're we're still working
hard to overcome this challengeof getting to lymph nodes. And
if we do that, it looks like wecan really help to train the
immune cells and equip them todo the right things and find and
kill cancer. So as we learnmore, as we we understand more
what makes a tumor tickessentially, we can develop
(22:36):
these types of treatmentsspecifically for different types
of cancers and go beyond eventhe KRAS cancers that we're
treating right now.
Dr. Moira Gunn (22:43):
Well, doctor Demuth, this has been terrific.
I hope you'll come back and keepus updated.
Dr. Peter DeMuth (22:47):
I look forward to that, Moira. Happy to.
Dr. Moira Gunn (22:50):
Doctor Peter Demuth is the chief scientific
officer of Eliseo Therapeuticson the web@elicio.com. That's
elicioelicio.com.
There are few things more anxiety producing
than having to go in and get ascan to see if your cancer may
have returned. And thankfully,scans do pick up tiny tumors.
But what if we could seecharacteristics of that cancer
much earlier while they weresimply individual cancer cells?
(00:32):
And what if that ability mightlead directly to a treatment or
even a vaccine, recognizing andeliminating those cells should
they appear in the future?Today, we learn how Elicio
Therapeutics is working to dojust that.
Doctor Peter DeMuth is its chiefscientific officer. Doctor
(00:52):
Demuth, welcome to the program.
Dr. Peter DeMuth (00:54):
Thank you. It's great to be here, Moira.
Dr. Moira Gunn (00:57):
Now I've been thinking about a place to start
and I'm hoping this is the rightplace. You know, we we've all
heard about DNA, but you use theterm ctDNA. What is ctDNA?
Dr. Peter DeMuth (01:10):
Yeah. That's a great place to start. So ctDNA
stands for circulating tumorDNA, and this is DNA that is
released by tumor cells thatmight be present in the body.
And some of this DNA, when it'sreleased, is able to make its
way into the blood. And then itcan be detected with a
specialized test that analyzes apatient's blood.
(01:32):
And these tests are reallyinteresting because they're
based upon a DNA signaturethat's found in the tumor. It's
specific for the tumor almostlike a fingerprint. So these
tests are designed to work bydetecting that DNA signature of
the tumor in the blood so thatif we see this fingerprint in
the blood test, it tells us thata tumor is present somewhere in
(01:56):
the body.
Dr. Moira Gunn (01:57):
Now is this new technology? Have we been using
it for some time? Where are wewith this?
Dr. Peter DeMuth (02:04):
It's it's relatively new. We're definitely
seeing progress, and these typesare types of tests are being
designed and perfected overtime. So we're looking to
improve the way that we candetect cancer using these ctDNA
tests, and the other reallyinteresting opportunity is to
use them to, inform thetreatments that we design for
(02:25):
patients. So taking a big stepback right now, most of the
time, cancer patients arediagnosed using medical imaging
techniques. And this can give usimportant information about a
tumor, can show it us where itis or how advanced it is, and it
can even be used once patientsare on treatment so that we can
(02:46):
monitor the tumor, and it cantell us whether the cancer is
responding to a particulartherapy.
Is it getting bigger? Is itgetting smaller? Is it
completely gone? So imaging isreally useful, but these ctDNA
tests could be used in many ofthe same ways to detect a tumor,
to learn something about thetumor, to understand if a
(03:07):
treatment is working, but thectDNA tests have some really
important advantages. So thismight help us to treat cancer
more effectively.
One of the big advantages isthat because ctDNA tests use
blood, they can be moreconvenient than going for
repeated medical imaging. Butalso, and this is the big one,
ctDNA tests can be extremelysensitive. So for example,
(03:30):
medical imaging might only beable to detect a tumor that is
about a centimeter in size, butsince ctDNA tests are based on
DNA, they might be able todetect the presence of a much
smaller tumor that would notordinarily show up on a medical
scan. And the reason this isimportant is because with
cancer, treating early when atumor is small and more
(03:53):
manageable gives us the bestchance to be successful. So,
overall, it's really exciting tosee these tests being used more
often and in different ways, andI think that could really help
improve patient care.
Dr. Moira Gunn (04:05):
Now do we have to know the tumor profile, the
tumor DNA for a particularperson to compare it to see it
in the blood?
Dr. Peter DeMuth (04:16):
Yeah. Many of these, tests are built upon, an
analysis of a tumor that's doneearly on when a patient is first
diagnosed, and then thatinformation is used to develop
the fingerprint that Imentioned, the signature of the
tumor, and that signature iswhat is analyzed in the blood.
So some of those tests are builton that concept, but others use
(04:38):
more basic information that isshared and common across many
different tumors in manydifferent patients.
Dr. Moira Gunn (04:44):
So let's say I have cancer surgery. If all the
cancer is removed, then weshould not see any ctDNA in my
blood. Right?
Dr. Peter DeMuth (04:54):
That's exactly right. So if a tumor is truly
completely removed by surgery orit's destroyed by a therapy
that's effective, there would beno tumor cells left in the body
to produce that ctDNA. And inthat case, the ctDNA test would
be negative. It would show nodetectable levels of ctDNA or
(05:15):
presence of that tumor signaturein the blood.
Dr. Moira Gunn (05:18):
And going on from here, if there are cells
that are remaining, will theycontinue to grow and we
eventually see their ctDNA?
Dr. Peter DeMuth (05:27):
Absolutely. And I can give you a really good
example of this. So one areawhere ctDNA tests are being used
is to evaluate patients aftersurgery. So, of course, the goal
of surgery is to completelyremove the cancer, but,
realistically, that can be verydifficult to do. So ctDNA can
give us a very sensitive tool todetermine whether there's tumor
(05:51):
remaining after surgery.
So if ctDNA is present, we referto that as molecular relapse. So
this is because we can see thesignature of the tumor on a
molecular level, And this isoften at a point where standard
medical imaging may not be ableto detect that tumor at all. So
(06:11):
by using this approach, we'veseen that patients with
molecular relapse after surgery,they're more likely to develop
that visible tumor on theirscans, and this happens much
more quickly compared topatients that don't have
detectable ctDNA after surgery.So having this information gives
us a really good opportunity totreat these patients earlier
(06:34):
when the overall amount of tumoris small and the goal, is to see
that ctDNA level decrease or,best case scenario, go away
completely. And if we're able toachieve that, the expectation is
that we could prevent recurrenceof the tumor and patients might
have longer and healthier lives.
Dr. Moira Gunn (06:54):
Now let's get to what Eliseo is doing. What are
you doing?
Dr. Peter DeMuth (06:57):
Yeah. So till now we've talked about how we
can determine the DNA signatureof a tumor as part of that ctDNA
test. But the tumor signature isimportant in other ways. For
example, it could give us cluesabout what parts of the tumor we
can target with treatment. Forexample, what parts of the tumor
differentiate it from normalhealthy cells, and these
(07:19):
differences could be really goodtargets for a potential
treatment.
So our goal at Alesio is to usethat information, that signature
of the tumor, to train theimmune cells of the body.
Essentially, we want the body'sown immune cells to use that
tumor signature to identifycancer cells specifically and
then to destroy them. And it'sprobably helpful to pause here
(07:41):
and say something quickly aboutthe immune system. When we talk
about the immune system, what wereally mean is the millions of
immune cells that are present inour bodies, and there are
different types of immune cells.Each cell type has a function
and a job, and overall, thesecells work together to protect
us from infectious disease,bacteria, from viruses, but they
(08:03):
can also protect us from our owncells if they become mutated and
have the potential to becomecancer.
So one of the jobs of the immuneresponse is to detect these
mutated cells and, ideally, tokill them before they're able to
become cancer. And oneparticular type of immune cell I
wanna mention is important forthis. Some people may know these
(08:25):
as t cells. But if not, what youneed to know about these cells
is that they patrol throughoutthe body. Part of their job is
to recognize the mutations thatdevelop in cancerous cells.
In other words, they coulddetect if a cell has that
signature or that fingerprintthat's associated with cancer.
And with the right training,they can search out and destroy
(08:46):
those cells. So to bring it allback, the idea at Alysio is to
design treatments that can trainthese immune cells so they can
first recognize that cancersignature and have the ability
to kill those cancer cellswherever they find them in the
body.
Dr. Moira Gunn (09:03):
So you're smartening up these t cells,
these immune cells, and they'retrans they're all over your body
looking. Looking looking lookinglooking.
Dr. Peter DeMuth (09:10):
That's exactly right.
Dr. Moira Gunn (09:11):
I feel like my body is so smart. Make your body
smarter. It could be your model.It could be your model.
Dr. Peter DeMuth (09:17):
We often call the lymph nodes the schoolhouse
of the immune system for thatexact reason. We're taking these
immune cells to school.
Dr. Moira Gunn (09:25):
Now you just mentioned your lymph nodes. What
do what do they have to do withwith these these immune cells,
these t cells you're smartening
Dr. Peter DeMuth (09:35):
up? That's a great point, Moira, and and I'll
get to that. Let me first startby talking to you about these
signatures a little bit more.One of the main signatures that
we're looking for in the cancersthat we're trying to treat is
called KRAS. KRAS is a mutationpresent in many different
tumors.
It's part of that tumorsignature. In fact, it's present
in about 20 5% of all humansolid cancers, including
(09:59):
pancreatic and colorectal andlung cancers. And in total,
these mutations affect cancersthat are present in 100 of
thousands of patients in the USevery year. So if we could
design a treatment that wouldtake those immune cells to
school, train them up so thatthey recognize that mutant form
of KRAS, these cells would thenbe able to go out and destroy
(10:22):
those cancer cells throughoutthe body. For for example, they
could be useful to to eradicatecancer cells that could be left
over after surgery and preventthose cells from growing and
causing recurrence of the tumor.
So let's get to the lymph nodes,as you mentioned. So training
(10:42):
these immune cells is a bigchallenge, and the lymph nodes,
we believe, are the solution tothat challenge. So the average
person might not think aboutlymph nodes very much, but
they're very important for theimmune response. These are the
primary sites in our body, wherethe immune cells come together,
where they exchange informationwith with each other. They serve
(11:04):
as training centers for theimmune response.
So in essence, where the immunecells coordinate all the
activities that they need toperform to defend the body. So
the strategy at Alysio is to getthese types of treatments to the
lymph nodes, and that has been abig challenge. Typically, these
types of treatments, afterthey're dosed, they're diverted
(11:24):
away from the lymph nodes, andso they might miss their chance
to train those immune cells. Butwhat we're doing at Alysio is
developing a new class, a newtype of treatment that are
targeted directly to the lymphnodes where we can train those
immune cells more effectively.And this is something that has
taken a lot of work.
And the strategy that we'vedeveloped is based on albumin,
(11:48):
this very common protein in thebody, which has a very useful
property in that it travels veryspecifically precisely into the
lymph nodes. So we're lookingwith our approach to take
advantage of this, and we can dothat by engineering our
treatments to attach to albuminafter they're injected, and this
allows us to directly targetthose treatments to immune cells
(12:11):
in the lymph nodes. So the ideahere is that once in the lymph
nodes, those treatments caneducate immune cells so they
recognize the tumor, and thosecells are able to patrol
throughout the body, searchwherever they find cancer cells,
they're programmed to kill them,and do that specifically while
leaving normal healthy cellsuntouched. And if we're able to
(12:33):
do that, we've got a really goodshot at at treating cancer
effectively.
Dr. Moira Gunn (12:38):
So you're taking albumin, which we've all heard
of, you know, is very common inthe body, and you're engineering
that signature onto the albumin,then the albumin goes into the
lymph node and says, hey, thisis what you gotta The back end
says, this is what you gottalook for. That's what's making
(13:00):
the t cell smart?
Dr. Peter DeMuth (13:02):
Yeah. That's exactly right. This is this is
all about delivery. We haveinformation that we wanna get to
the immune cells, and albumin isable to get that information
directly into the place wherethe immune cells are are where
they are and where they can usethat information to develop the
right responses to treat cancer.
Dr. Moira Gunn (13:19):
So you're also making smart albumin?
Dr. Peter DeMuth (13:22):
Well, albumin is already smart. You're just
taking advantage of the thingsit knows how to do really well.
Dr. Moira Gunn (13:28):
Alright. Alright. We're there. Now, I
know you're in phase 2 forpancreatic cancer. Every phase 2
started with a phase 1.
Let's take us back there so weknow what you did in phase 1.
Who you looked at, the humansyou looked at, what you tested,
and what you learned.
Dr. Peter DeMuth (13:47):
Yeah. So I'd love to do that. The phase one
trial was looking at 25 patientswith pancreatic and colorectal
cancer, a group that is insignificant need of new
therapies. These patients hadalready been through the
standard treatments. So in thiscase, that's chemotherapy and
surgery to remove their tumor.
And after that, they'reevaluated using medical imaging
(14:12):
to understand the state of theircancer. We're essentially
looking to see if we can findany tumor remaining. And for
patients coming on to the trial,the answer there was no. The
scans didn't show anything. Wecan't see a tumor, but, this is
a big but, when we look withthat more sensitive ctDNA blood
test, we see the tumor.
We're able to see that thosetumor cells are still present,
(14:34):
and, unfortunately, this meansthat the cancer is likely to
return and at that point toprogress really quickly. So with
this information, what we askedwas, can we treat those patients
to eliminate the remaining tumorcells that we detected with the
ctDNA test? And by doing that,could we potentially prevent the
(14:54):
cancer from returning? So that'sexactly what we tried to do, and
we saw some really interestingthings. So the the first thing
we saw was the immune response.
We, in this case, wanted tocount, essentially, to count the
number of tumor killing immunecells that were present in these
patients before and after thetreatment. And what we saw was
(15:14):
that after treatment, the numberof immune cells was increased in
the vast majority of thepatients on that trial. So,
obviously, this suggests thatthe treatment is doing a good
job of training up those immunecells. After that, we wanted to
see whether patients hadreductions in the level of their
ctDNA, and we saw that that wasthe case in many patients. In
(15:36):
fact, almost a quarter of thepatients completely cleared
their CT DNA, which means itwent to 0 undetectable.
And so that is suggestive thatthe residual tumor cells that
were present after surgery werebeing killed. And what's really
exciting, the last thing wewanted to do was see whether the
strength of the immune response,the number of immune cells, was
(15:58):
in any way connected to how wellpatients did overall. And so
what we did is we looked at thetime that patients would take to
relapse or to pass away fromtheir disease and measured that
against the strength of the tcell, the immune cell response.
And what we saw was that therewas an 86% decrease in the risk
(16:19):
of recurrence of death orrelapse in patients that
developed the strongest, thebest immune cells to our
treatment. So this is obviouslyreally exciting, and it shows
that the treatment is bothgenerating those immune cells,
training them up, and that ifpatients get those types of
responses in their immunesystem, they may be able to
(16:41):
delay or prevent the return oftheir cancer.
So, obviously, now our job is toconfirm that in the phase 2
study.
Dr. Moira Gunn (16:48):
And as happens in phase 2, you look at what
happened in phase 1, and youdon't just continue it. You say,
okay. Maybe we'll target this ormaybe we'll change this. And so
while you will, at some point,work on colorectal, you decided
in phase 2 just to focus on thepancreatic cancer. Now tell us
what that is and how that'sdifferent.
Dr. Peter DeMuth (17:10):
Yeah. That that's exactly right. So the
phase one look at both. We haveto make a choice in phase 2, and
we chose to look at pancreaticcancer. And there's some good
reasons for that.
We know that pancreatic cancersare often mutated with this KRAS
mutation, so they have the exactsignature that the treatment was
designed to address. So manypatients with this type of
(17:31):
cancer could benefit. We alsoknow that pancreatic cancer is
one of the deadliest cancers. Ithas a 5 year survival of less
than 20%, so patients are in invery great need of new
therapies. So in this trial, thephase 2, we're again looking at
pancreatic cancer patients,again looking at patients that
(17:52):
have completed their standard,treatments, either chemotherapy
or surgery, both most likely.
And, again, the standardapproach here is observation. So
doctors are just waiting.They're monitoring. They're
looking for that tumor toreturn, and they know that it
will. So in the trial, insteadof just waiting, instead of just
(18:13):
watching, we're gonna look tosee if this experimental
treatment can delay or evencompletely prevent the return of
the tumor.
And, again, because this is aphase 2 study, we'll have the
opportunity to compare theoutcomes in those patients, the
ones that get the treatment, tothose who receive the standard
observation. And this will allowus to measure how well the
(18:36):
treatment works.
Dr. Moira Gunn (18:37):
And how many people are in that study?
Dr. Peter DeMuth (18:41):
Approximately a 135. So patients will be split
to either get treatment or toget observation, and then we'll
be able to follow them again tolook for the amount of time that
it takes for patients to have arecurrence of their tumor or to
pass away, and that will give usa chance to observe the benefits
that we could potentially seewith this treatment.
Dr. Moira Gunn (19:02):
And if they're not getting Eliseo's treatment,
they're still getting all theother treatments that they were
Dr. Peter DeMuth (19:08):
That's exactly right. Be.
Dr. Moira Gunn (19:10):
Designed to be given. Yeah.
Dr. Peter DeMuth (19:11):
Exactly.
Dr. Moira Gunn (19:11):
So no one is without treatment in this?
Dr. Peter DeMuth (19:14):
That's exactly right. Yes.
Dr. Moira Gunn (19:15):
That's great. Now you keep saying if they got
the treatment. Is this a onetimedelivery?
Dr. Peter DeMuth (19:21):
So the treatment is, multiple doses. So
we give 4 doses in the 1st monthand 2 additional doses in the
2nd month. And so this is theinitiation, the first the first
training session for the immuneresponse, if you will. And then
we give those immune cells alittle bit of a break, and then
we come back in and we trainthem again. We give them another
(19:42):
4 doses.
So, essentially, another lesson,another, another session to
learn the the lessons that we'retrying to teach them.
Dr. Moira Gunn (19:50):
So, you know, this really is science. We have
to figure out how much is toomuch, how much is too little,
how much is enough. There'sthere are questions here.
Dr. Peter DeMuth (20:00):
Absolutely. Yes. There there are tons of
things we're still learning. Oneof the really interesting
questions here is how manyimmune cells we need to be
effective? Also, what sort ofqualities or functions those
cells need to have in order tobe effective killers and finders
of tumor cells in the body.
And I think the biggest thingthat we're most interested to
(20:21):
study, and that's the main goalof the phase 2, is, again,
whether this type of treatmentcould prevent the cancer from
turning from returning, and ifso, how long that that
protection might last.
Dr. Moira Gunn (20:33):
So this starts out as a treatment because
you're treating cancer that ispresent. And if it prevents it
in the future, it becomes avaccine.
Dr. Peter DeMuth (20:43):
That's exactly right. So this can prevent the
return of cancer in the future,but it certainly starts out in
your body as a treatment. Andthis is one of the most amazing
things about the immune system,essentially that it has a
memory, that it can remember thepast dangers that it's
experienced before. And this isreally important because it
(21:04):
means that the immune cells thatremember can react more quickly
to protect you from threats thatyou might see again in the
future. So, certainly, whilethis treatment is designed to
address cancer that's presentnow, the immune system can form
that long lasting memory, and itmight be able to recognize
future cancer cells and thenprevent them from returning and
(21:24):
causing the disease to progress.
So it's certainly a reallyexciting opportunity to treat
patients, but also to give thempotentially really long lasting
and durable freedom fromdisease.
Dr. Moira Gunn (21:37):
So any future cancer with a KRAS mutation,
hopefully, it would say youmight be a completely different
cancer, but we have you. Butthere are other mutations and
other unique mutations.
Dr. Peter DeMuth (21:50):
Yeah. Absolutely. There are many
different mutations. Cancers arevery diverse. So this is the
type of therapy that could beused to target those other
signatures of the tumor, andthat's kind of the exciting part
looking into the future.
We're learning how to trainthese immune cells. We're
teaching them how to see tumorcells behind them and destroy
(22:13):
them. We've worked really hard,and we're we're still working
hard to overcome this challengeof getting to lymph nodes. And
if we do that, it looks like wecan really help to train the
immune cells and equip them todo the right things and find and
kill cancer. So as we learnmore, as we we understand more
what makes a tumor tickessentially, we can develop
(22:36):
these types of treatmentsspecifically for different types
of cancers and go beyond eventhe KRAS cancers that we're
treating right now.
Dr. Moira Gunn (22:43):
Well, doctor Demuth, this has been terrific.
I hope you'll come back and keepus updated.
Dr. Peter DeMuth (22:47):
I look forward to that, Moira. Happy to.
Dr. Moira Gunn (22:50):
Doctor Peter Demuth is the chief scientific
officer of Eliseo Therapeuticson the web@elicio.com. That's
elicioelicio.com.
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