M. GALVAO NETO New totally transoral endoscopic treatment for morbid obesity, type 2 diabetes and G

Thank you for the invitation, and in my name and the name of my team, I would like to present

to you our experience with the endo-barrier, that is endoscopic endoluminal, duodenal bypass.

Can we pass the next slide, please?

Yes, I move to the next slide.

This slide is about my disclosure, and this is my potential conflicts of interest

for this presentation. Next slide, please.

Okay.

And on this next one, this is the topic and advance to you that is a lot of

experimental and basic science background on what we are about to discuss.

We can go to the next slide.

Okay.

This slide is about the background, specifically on pigs that we have

have developed delivery system, the compatibility of the sleeve, the station of the sleeve,

how much far we can go into the jejunum, the stiffening of the anchors and lots of things

that we can see on the next slide, please, that up to 08, and now it's much more, we

We had 470 animals implanted, that means 900 months of studies and almost 75 years of pig

life, almost six tons of food surviving animals from one day to one year.

We can go to the next slide.

And this was published in an article on surgical endoscopy, how all the pioneers on that managed

that on animals until we get on people. On the next slide, please.

Okay.

Now it comes some very strong evidence that we can use the endoluminal

sleeve to treat diabetes. This is a paper coming from Harvard from the

group of Lee Kaplan. And we can see on the next slide, please.

Okay.

In this next slide, you can see here in the numbers 1, 2, and 3 that they had used the

same kind of material that we use in humans, and they had implanted this leaf with the

same anchoring system that we have used in humans.

In rats, those rats, a model from them, and they are morbid, obese, diabetic rats, diet

induces. It means it's very close what humans like. On the next slide please.

Okay. You can see here the endoluminal sleeve ELS and you can see two lines

and one is the sham-controlled rats against the endoluminal sleeve. This is a

mute tolerance test in terms of glucose and you can see that the endoluminal

sleep had almost a normal behave when compared with control sham group next

one please okay also data coming from the group say that the energy spenders

when we use ruin why models of rats the energy spenders just having a win-win

white procedure is more than a sham control group.

Next one please.

And this is data from Catholic University that have done some work with Harvard also.

And you can see here that the endo barrier and the energy spender, and you can see on

the left resting in total, you can see that the rest with the sleeve had a higher, much

much higher energy expenditure when compared with the sham control group.

Next one, please.

Okay.

This, we will begin about the technique of this procedure.

The next slide, please.

Okay.

So, what we talk now, we are talking about an impermeable liner that is anchored

in duodenum, has 60 centimeter lungs, is endoscopically placed and removed, provides a duodenal

and we have targeted trials and studies on type 2 diabetes mellitus and weight loss.

So we have over 430 patients since 2005 treated.

We have achieved now the milestone of 500 patients treated with this technique.

We can go to the next one please.

In these specific slides, what we see is the sleeve itself.

On the first slide, the bigger one, the picture on the left, we have the whole liner that

is made from a material like Teflon, PTFE, have 30 micron and is impermeable.

On the right, the small picture, we can see the anchoring system that is made of nitinol

and have lots of barbs to be stable in the duodenum and on the next picture on

the right we have the whole delivery system that's kind of complex but is

very stepwise on its delivery. Next slide please. Okay. On the next slide we this

series of slides we will try to explain to you how we implement it. So this very

very first you can see the scope on black, on the tip of the scope we see a guide wire,

so we just pass a guide wire as far as we can, next slide please, and over the wire

we slide a catheter that has a capsule on its tip, and you can clearly see that there's

a white capsule with a ball halfway into the duodenal bulb, you can go to the next slide

between the stomach and the duodenum, the pelopylorus, and you can see going out of

this the whole sleeve that was standing up to 60 centimeters into duodenum and this is

a radiological part of the procedure that you slide and you advance it and you feel

the bowel movement and you can advance over the bowel and you can see the bowel on the

tip of the sleeve. Next slide, please. Once we span the whole sleeve, we get rid of the

ball and the ball will pass through the ball with no problem, we will rearrange the capsule.

You can see now that the white capsule is rearranged and get back a little bit into

the stomach, so on the position to deliver the stance. Next slide, please. On this slide,

just after the white capsule you can see that the stand is completely open so

once it's done we will remove the inner catheter we move the capsule next slide

please okay okay this light you can see that it's fully standard the the sleeve

next slide okay on this next slide you can see that the capsule is detached

it from the whole system and this is the system that will stay in place.

Next slide.

Okay.

This slide is like a proof of concept that the food will pass into the sleeve avoiding

contact with the proximal bowel.

We can see on the picture on my right that you have a radiological test that

you can clearly see that the folds are on longitudinal way instead of the

transversal way that we will find on the bowel. And this means that the food is

passing into the sleeve. On the inferior left you can also see endosomogram

showing us as three month implants and we can see the growing of the

mucosa layer. On the top figure we see the stand fully open. I

think we can go to the next one. This is a concept slide so you can see

You can see on yellow food you can also see in light white the sleeve fully

standard.

Next slide please.

Okay.

And on the next slide you can see that the biliopancreatic juice is passing

along and outside of the sleeve and they will merge with the food 60 centimeter

after.

It is in this mimics a biopancreatic limb of a Roux-en-Y gastric bypass.

Next please.

Okay.

Those will be about removal.

Next please.

Okay.

So removal is a little bit tricky because we have an implant in a post-pyloric

historic situation in the duodenum and has a lot of bumps that can damage the tissue

on removal.

So what we use, we use a cap on the tip of the skull.

Next one please.

Okay.

You can see the cap and we have a customized grasper that grabs one of the sutures

tissues around the prosthesis, next, that will collapse the anchor, next, please, and

we will advance the collapsed anchor into this hood, so you can see that the hood on

the tip of the scope is protecting the tissue, next, please, and on this next one we can

can see how we remove it, like a big tanya or something like that.

Next slide, please.

Now we have the slide about procedural comparison.

Yes, sir.

On that specific slide, we in one can compare on the left and on the right.

On the left, we have a renal bypass.

bypass. And if we get into the the whole picture of the biliopancreatic limb that

is on mostly begin on blue and then merge blue and green arrows you go to

the next figure on the right and you can see how the sleeve can mimic the

the biliopancreatic limb. Next slide please. And on this next slide we

even more clearly see that comparison on that. On the next slide please.

One can see if you compare procedures surgical procedures with the endo

barrier. So you can see that on the far right below endo barrier name you can

can see that it induces an increased resistance to the gas emptying, and also

it bypasses the duodenum and jejunum as Roux-en-Y and BPG do, and it exposes somehow

the jejunum to undigested foods.

Next please.

So we are about to begin on telling you what is the experience

we have on clinical trials with this device.

It all begins, next please, in Chile with Dr. Leonardo Rodriguez in Chile

that we had the first experience and we target safety and some efficacy.

It was a three-month trial that was published in Sword magazine

magazine, and it has 28% excess weight loss, and very encouraging results that leads to

the other trials.

Next one, please.

Okay.

So the initial American experience was also published with Dr. Kiftberg-Kersing.

Next one, please.

Okay.

We can see here on that one that the trial evolved in a more elegant way in terms

of statistics with an open-label perspective, randomized controlled trial against diets,

and this, again, was in Chile, in Catholic University, in Debreca Hospital.

Next one, please.

Okay.

And on the same time, almost the same time, the Europe experience with Dr. Grieve

group in the Netherlands.

They have done a multicentric randomized trial targeting pre-surgical weight loss.

Next one, please.

Okay.

By the time the small trial that was done in the U.S., that was a very pilot trial,

that was done with lots of very known authors like Kikersen, Rostin, was

published. Next please. We had the opportunity with Andy Levine that to show

that getting cases all over the sites of what's doing that radiographically we

we could prove that the liner is impermeable.

Next please.

Okay.

And then we got on this very first diabetic study, it was a prospecting randomizing

sham control trial, that is a very elegant way on showing the efficacy of these on treating

diabetes.

Next one please.

And this was very recently, published online, this is our work on Sao Paulo University,

led by Dr. Eduardo Moura, and it was patients, morbid obese diabetic patients,

and a subset of group got into one year.

So this expose was all about the trials.

Next, please.

And we also want to share with you some of the results that we have.

Next, please.

Okay.

Results coming from America and Europe as you can see here.

Next please.

This is delivery learning curve meaning that how many time we need to implant the device.

You can see that the learning curve is very well established and now we have around 25

to 35 minutes to implant.

Next please.

Okay.

On the next one you can see the retrieval curve that is even faster, now around 10 to

15 minutes to retrieve the device.

Next please.

From the weight loss perspective we can see here some South American data and in the interrupted

lines there are control groups and we can see on the full lines the treatment groups

loops, and you can focus on 12 weeks, and you can see that it's around 25, 26 percent

assessed weight loss, but the curve continues on the trial, on the blue full line, and you

can see that we reached 30 percent assessed weight loss.

Next please.

And this, again, is total body weight loss instead of excess weight loss, but has more

trials. You can see in the line, the control groups on the top of the chart, and we see

a downhill lines of all the studies, and you can see here Europe device, and going down

have the sites. That is Brazil device and Chile device on 52 weeks, meaning one year.

So, around 17 to 20% of total body weight loss is very acceptable.

New data coming from Chile, one year, and you can see here, are we on the site of weight

loss one year?

Yes, yes we are.

That's nice.

So, we can see here on the left BMI, on the right excess weight loss that the Chile group

group, on one year 46% of excess weight loss.

Next please.

Ok.

Very interesting, some very few patients was targeted and this is a very full

slide but I will try to explain it to you, it's a post explant weight regain pattern

that you can see here on the bottom, on week 52 was explanted those patients and they regained

some of the weight but very much slower slowly than we expected next please okay also there's

some a very uh preliminary experience on adding some restriction to uh to the the whole sleeve

next please okay that was first presented at poster and on the left we can see what

what I mean. It is mean that we just close the whole stand leaving a hole on the middle

narrowing the passage of the food. Next please. That's about the animal experience showing

us that with five millimeter orifice we do not have much efficacy. Five millimeter was

millimeter hole that doesn't just allow this to pass next please so was very

quickly ten subjects three months study but more important next please okay and

you can see here on that slide that is a bariatric population for BMI mean of

of 40.8.

Next please.

Okay.

Interesting on this trial is that on 12 weeks when we achieve it around 20, 25%

with the previous device, we achieve it almost, you can see here, 40%, 39.6% excess weight

loss on 12 weeks, it's very encouraging.

Next please.

Next please, here you can clearly see the line on the bottom is the regular endo-barrier

that we use, and on the top we can see the endo-barrier with the restriction and we can

compare different results benefiting the restricted device.

But the experience is very limited on this specific type of liner.

You see again that the lines get closer, meaning that the change that we made on the gas emptying

was not definitely and was fully reversible, and this is very interesting to understand.

Next please.

Okay.

But, and everything that's so good has always a but, most of the patients we can

see here, 7 on 10, require endoscopic dilation, and maybe the 4 millimeter hole was not the

the ideal one, and we have to dilate most of those patients.

Now we are talking about what is clearly the interest of this device now, this type 2 diabetes.

And I'll get into the first study that made Hospital de Breca Chile by Dr. Leonardo Rodriguez,

And all of this study, we have the honor to be co-authors and participate on that.

Next please.

Okay.

This study was presented on American Diabetes Association in the Inquitins session

also.

Next.

Okay.

As we can see on these slides.

Next please.

Okay.

And this was published on Diabetes Technology and Therapeutics.

Next please.

Okay.

This is to show you that we have three lines here on demographics.

We have it all as the first row, as the first column, and we can see also the DGBL, meaning

the duodenal gestational bypass liner, 12 patients, and six sham patients.

How sham?

it means that every single patient got an endoscopy but they were they were not

aware which one of themselves has the liner so we can see here and if we can

compare that no significant in between the two groups in terms of casuistic

next please okay and this is was more the most

impressive thing that we find on this trial on the left you see the end of

barrier subjects.

On the right you have the sham patients.

And you can see here on the bottom that the area under the curve on the tolerance meal

test on group and barriers, we have 19 percent of improvement.

And if you compare with the sham subjects with best medicine possible, they have a worsening

in 10 to 8 percent, it was significant.

Next please.

and if we follow the line are we on the fasting glucose glucose are we connected

yes yes we are okay so we have two lines here and you have the full line the

liner and the the whole the superior line with sham and we can clearly see

that the liner over the 24 weeks had got better results with best medicine next

Next, please.

Okay.

This is a very busy slide, I want to pass it, please.

Next, please.

Okay.

This is the light that shows us very clearly the results.

We have here the H1BC that when we compare with week 12, we have 1.3 on the liner group

against the 0.7 on the treatment group.

When we go to the right, on the 28 weeks, last visit of the patients, we have minus

2.4 on H1BC, on the liner group, on the endo-barrier group, when you compare with the best treatment,

best medicine possible group that have 0.8.

It's a very clear difference in the prospective randomized sham trial that has downsides that

was a very small sample but we for very interesting results next please okay and

that's the study done in Brazil so far University we are also co-authors the

main author is Dr. Eduardo Moura next please okay this study is about morbid

obese diabetic patients next please okay and this is the results we have up to 24

four weeks you can see here that h1bc get down from 8.4 to 6.9 over over the time next please

okay and in a subset subset of 13 patients that already got 15 two weeks we get even better

from 8.9 to 6.6 and you can see that standard deviation is not that big next please

This also, this treatment also has a favorable impact on the metabolic

syndrome that we can see here, I'll go top to bottom, on the weight significant,

on the BMI significant decrease, waist circumference significant decrease, blood

pressure, they were not significant, the cholesterol, almost all of them were

significant specifically is in more triglycerides glucose as we can see

insulin insulin resistant by HOMA and even they were h1bc that we already have

disclosed about it next please okay and this is about the study that we

just finished all the implants and we will remove the one-year patients they

They are, next please, as all of these studies, they are IAB approved studies, and this study

is about what we call lean type 2 diabetes patients.

They have BMI between 25 and 30, and next please, all of these patients had already

been implanted.

We will remove the one year implants on June of this year.

The results are very, very favorable.

I do not have them yet because it's an ongoing study.

Next please.

Okay.

So about adverse events, we expect in most of the patients, almost all the patients

patients have early nausea and pain, and that usually self-limits and are mild about first

and second week, and after that, they go away and they can appear when the patient got on

dietary indiscretion.

Next please.

Okay.

So we had a lot of improvement in terms of adverse events, so we can see here on

that slide migration and movement we go down from 43 from the first studies to

three percent and less on with the improvements on the anchoring system the

barb system that we put the the company has been able to produce a more stable

anchoring system next okay also the GI bleeding we with the adding the

The intensive use of PPIs, they really, really go down.

And most of all of them, except for, sorry, most of them were handled endoscopically.

And all but two were self-limiting.

Those two that was not self-limiting needed endoscopic therapy locally.

Next one, and I think this is the final one.

We can hear that we have treated more than 400 patients in 11 trials, and we had immediate type 2 diabetes improvement.

The improvement on diabetes is related with the time to stay in place.

And on the second-generation device, we got more stability.

The safety of all this study was with very low severe adverse events, and this is what

we had to tell you about this five-year experience with the device, that we had the opportunity

to be present at least on the half of those implants and have the opportunity also to

to be part of most of the trial, and we would be more than happy to answer any question.

Thank you very much.

Thank you very much. Thank you.

So I would ask, first of all, to Professor Costamagna if he has a question related to this topic,

because he works very much on that.

Thank you. Thank you, Dr. Neto, for your nice presentation. Very interesting.

Of course, the principle that was firstly tested in rats by an Italian, by Rubino, published

in Annals of Surgery when he was working at the ERCAD in Strasbourg, is fantastic.

What I think is still very debatable is the device.

the implantable device will lead to some complications that the history of surgery and the history

of endoscopy so I think that this is the first limitation if we could imagine to find the

solution without implantable device to have the same bypass of the first duodenal and

jejunal loop of course it would be fantastic the second problem that I see of course your

results are very very nice and I think that a little bit too much optimistic

because we know that after removal of the implantable device this is the

experience with the with a balloon people morbid obese patients are not

cured because so they will regain weight so I think we should wait a little bit

more to see what happens in patients that after removal of the of the device

and third thing if I remember well you mentioned that now the time the devices

can be in situ is one year did I did I hear right because at the beginning was

three months or six months yeah it's one year right which of course is better and

And again, the makers of the device should be congratulated

because having insight for one year is a long time.

Nevertheless, I have still this question to ask you.

How do you think you could improve the system, the principle, as a whole method?

Thank you very much for your questions.

It's a very clever one.

I can, as a matter of debate, return that when youth professors see problems, I see opportunities.

And we had technology is a very beautiful thing because it evolves.

So you completely agree that the first results were not acceptable,

acceptable, but it was the way we could learn on how to get stable on that ground.

And we learned that the problem was not to engage the barbs into the muscular layer and

stay there.

The problem is that after three months, the mucosa, it grows a lot, and the barbs that

you get engaged on the muscular did not stay there anymore.

more. So that whole learning led to a change on the technology, because now we know that

we have to develop stability on a very unstable ground. So concepts like how an Eskimo can

stay stable on the snow, or like a car that raced on a rally on sand, how they can be

stable in that unstable world.

And that's, all of these concepts were used to improve the stability up to one year.

And I'm very happy to tell you that this device got cleared on CE Mark for one year, and they

are now being used for, with this clearance of CE Mark in Germany, and I think in UK,

UK, and Spain, and I think very soon it will be able to have access on Italy, on that.

And the very other interesting that we not published but we already have some results

is after removal.

So very interestingly, Professor, after the removal there's some residual effect that

lasts up to three months in diabetes.

diabetes.

So it means that's very interesting.

And the other things that you probably know that our group have published, some experience

with the Rubino procedure, the duodenal gestational bypass, surgically done by laparoscopy.

And what we and the other authors that have done this technique, what we saw is just after

six months, as the patient stabilized or started regaining weight, the diabetic effects, it

it stops.

And with the liner, the indoor barrier, it's still running up to one year.

So we don't know yet what is happening.

But we are clearly very, very happy with what we are seeing.

And I can tell you that now most of the adverse events are very highly controlled.

And I think that now it's kind of safe.

I don't think it is now for everybody to do that, but it is very useful on one-year periods.

Okay, so thank you very much, Manuel.

I really appreciate your efforts to be with us today.

Compliments for all your work that you are doing.

I'm following you, and I hope to see you soon in person very, very soon.

So thank you very much.