A new strategy in the war on obesity

In this episode, Kevin Folta interviews Dr. Erik Ingelsson about innovative RNA-based therapies for obesity, focusing on the potential of silencing RNA and gene editing to target visceral fat and improve metabolic health.

What is Talking Biotech with Dr. Kevin Folta?

Talking Biotech is a weekly podcast that uncovers the stories, ideas and research of people at the frontier of biology and engineering.

Each episode explores how science and technology will transform agriculture, protect the environment, and feed 10 billion people by 2050.

Interviews are led by Dr. Kevin Folta, a professor of molecular biology and genomics.

Kevin Folta (00:03.871)
Hi, everybody, and welcome to this week's Talking Biotech Podcast. Now, across the globe, obesity is exceeding 15%. It's increasing. And it's a real big problem here in North America and sprinkling in other places as well. Obesity is far more than just excess adiposicity, more than just fat, right? Research over the last decade has shown that it creates a systematic metabolic state change that's deleterious.

pathologically, it drives chronic low-grade inflammation, cellular dysfunction, serving at high risk comorbidity, things like type two diabetes, athrogenic cardiovascular disease, non-alcoholic fatty liver disease, all kinds of things that it does, in addition to just the extra weight and extra plumbing that needs to maintain it. Intervening in primary hepatocyte dysfunction isn't optional. It's a it's a physiological imperative to halt downstream.

Cardiometabolic complications. But the good news is that there's a lot of new and emerging technologies to combat the fat, innovative drugs, and drug targets that have come a long way since grammar's amphetamines. So today we're talking peptides, we're not talking peptides. Today there are peptides like GLP1s that dominate this discussion. But there are some additional strategies on the horizon, and this is really exciting stuff.

I'm speaking with Dr. Eric Engelson. He's the chief science officer of Wave Life Sciences. So welcome to the podcast, Dr. Ingelson.

Erik Ingelsson (01:37.368)
Thank you, Kevin. It's great to be here.

Kevin Folta (01:39.594)
Yeah, so this is really cool. I really enjoyed studying up on what your company is doing here, especially in this wave 007 thing here. But let's talk about this first. we hear a lot about GLP1-like drugs and the amazing impact that they've had. I mean, it's really been pretty remarkable. But the approach has some drawbacks that must be considered when we look at these products. And so, what are some of the other collateral issues that we really don't discuss very often?

Erik Ingelsson (02:09.74)
Yeah, that's a great question. And I I guess I should first say that, you know, someone that has been working in the obesity field for a couple of decades, the GLP ones and other incretin-based therapies have really changed the whole landscape very dramatically. That said, they have some significant potential challenges. And first of which is really kind of they you lose an overall weight rather than the fat.

Which is what you want to lose, meaning up to 40% of your weight loss really comes from loss of muscle. And that is a bad thing for several reasons that we can get into later. They also have additional challenges, such as frequency in terms of dosing. You have to take injections very frequently. There are also poor tolerability, especially with gastrointestinal side effects that the majority of patients really experience.

So all of those things together lead to very high discontinuation rates. So if you take you know, individuals that have started with an increase in therapy, around seventy percent have stopped their therapy within a year. So so there are multiple opportunities to come up with new solutions here that focus more on the fat loss, with retaining the muscle, less frequent injections and without those tolerability challenges.

Kevin Folta (03:29.717)
No, very good. And you're using some other terms in here that maybe we should define. But could you touch on, you know, the idea of what incretin is in terms of the class of drugs?

Erik Ingelsson (03:39.085)
Yeah. So these these classes of drugs are generally focused on appetite regulation plus to some extent uptake from the gut. So the GLP ones that are well known, but all of these kind of similar drugs, they're all acting in similar ways, where they're primarily acting on appetite and caloric restriction. so we think there is an opportunity to to develop something that has a direct effect on the fat instead.

Both because it could circumvent some of those challenges with incretin based therapies, but also because it's a totally entirely different approach and you can potentially combine it with existing incretin drugs as well.

Kevin Folta (04:17.515)
And there's also the issue that there's different kinds of fat that we're talking mostly here about visceral fat, which is more metabolically toxic than subcutaneous fat. So, you know, what are some of the differences that you observe and why is one more important than the other?

Erik Ingelsson (04:25.582)
Mm-hmm.

Erik Ingelsson (04:32.396)
Yeah, so this is something that is well known for a long time. That the type of fat matters. So the fat that sits around your organs in your abdomen, that's called visceral fat. That is really the dangerous fat. That's the fat that is metabolically active, it's it it causes inflammation, it causes type two diabetes, it causes atherosclerosis. So so that's the type of fat that is most important to decrease. so our approach has a large effect on the visceral fat.

But also on the overall subcutaneous fat as well. So you you need to kind of have an effect to both to to lose weight and to to decrease your fat. But the visceral fat is really what's the most dangerous for future cardiovascular disease and type two diabetes.

Kevin Folta (05:14.805)
When you started out today, we talked about GLP drugs and the GLP one-like drugs, that they affect lean muscle mass, which is not an objective of of affecting the healthy part of weight loss. So, how do your drugs, especially this WVE007, how does that decouple fat loss from muscle wasting? And why is preserving that lean mass

Erik Ingelsson (05:21.518)
Mm-hmm.

Kevin Folta (05:42.429)
So critical to long term resting metabolic rate.

Erik Ingelsson (05:45.943)
Yeah. So traditional ways of losing weight, regardless of whether it's actually within GLP one or other incretins, or just by eating less, you would lose proportionally up to forty percent of your weight from the muscle. Now, the way to circumvent that is by not at acting on appetite, but instead having a direct effect on the fat cells. So what what this approach is doing is basically releasing a break

on the fat breakdown, or in other words, it's turning on more breakdown of fat directly in the fat cells. So it basically increases your fat burn if you want, or the metabolism of triglycerides. It's a type of fat that sits and stores energy in the fat cells. And by doing it that way you're circumventing any effect on muscle.

Kevin Folta (06:36.533)
Yes, so why are there breaks in the first place? I mean, if if visceral fat has a negative effect on physiology, why does the body keep it?

Erik Ingelsson (06:45.794)
Yeah, so this is this fascinating and it's a great question. So this is something that has been selected for throughout millennia of human evolution. You have to have stored your energy because it's the most efficient way of storing whatever you eat for the winter. So so th this is kind of a very important system for humans, like throughout our evolution until this last century, where

It's clearly not a good thing because now you have abundance of energy and and it's not a good thing to store all of that energy in your fat cells.

Kevin Folta (07:22.485)
Yeah, so it's a really interesting question. And that there is this mechanism and it seems like kind of a a switch that will allow it to dissipate. And so let's talk about that. So this all v boils down to the INHBE gene. Is that how you refer to this thing? Is yeah. In the inhibit gene. And how how how did this be it sounds like an island in the Caribbean.

Erik Ingelsson (07:39.81)
Yeah, we we usually say inabini. inabini. Yeah, in abene, yeah. Inhibini, yeah.

Erik Ingelsson (07:51.117)
Yeah. Mm-hmm. Yeah, so it's a actually it's a very exciting story, I would say. So like especially for someone with my background and work for a long time, both in obesity and also in human genetics. So this is this is a drug target and a mechanism that was discovered originally based on large population studies where individuals had undergone like sequencing of their DNA, basically. And it's

Kevin Folta (07:51.122)
how does this become a candidate?

Erik Ingelsson (08:17.866)
originally from a big study in the UK called the UK Biobinks. It's a half a million individuals that have been sequenced and then they have we have a lot of medical information on these individuals. So basically what we have observed is that these there are individuals in that database that lack a copy of the gene, if you want, or rather one of the two copies is not working as intended. We call that a loss of function variant. So basically they had just half of innovine

and they are protected from cardiovascular and cardiometabolic diseases. They have less of the visceral fat, they have less of like they have better lipid profiles, they have lower risk of cardiovascase, type 2 diabetes, they have less mash signs, so less fat in the liver as well. So generally look very healthy and kind of ideal state. And and again, what we know is that these individuals they have just one copy of that functioning gene. So they so they have less of that gene.

And less of the corresponding protein. So that's really what we're getting after then. What we're then doing with our approach is that we're mimicking this human genetic situation. So we're trying to remove at least half of that protein. And by doing that, we the intent is to mirror that profile that these individuals have with a less abdominal and visceral fat, you know, lower lip, like better lipid profile, better mash, so less.

fat in the liver and lower risk of cardiovasces and type two diabetes.

Kevin Folta (09:51.308)
Okay, so so the inhibid gene encodes this thing called activin E. And and so how does that protein work? What is it doing in the what's its role in adipose adipose tissue lipolysis? and how does that affect visceral fat?

Erik Ingelsson (10:09.292)
Yeah. So it's basically a break on the lipolyses. So this protein called active in it goes out in the circulation, it's produced in the liver, and then goes out in the circulation, and then it dimes to fat cells. And it sits on the fat cells and acts as a break. so as a way of storing energy to the earlier discussion we had. And then by either genetically you have less of it, or by introducing our approach to decrease it.

You're basically removing the break. So you're taking off the break of of this fat burning. or in other words, that leads to more fat burning in the fat cells.

Kevin Folta (10:45.055)
Yeah, so just to kind of clarify, so this activin E gene, a protein, which is encoded by the inhibiting gene, is the breaks of the process that this binds on the fat cells and makes them less likely to for lipolysis. So it it so so if you take this thing away, you now remove the shield that keeps fat cells as fat cells, right? So so far I got it, right? Okay, so.

Erik Ingelsson (10:51.534)
Mm-hmm. Mm-hmm.

Erik Ingelsson (11:08.856)
Yes. Yeah. And well th there's still gonna be fat cells, but you remove the break on the breakdown of fat. So like they shrink and they start like sending out the fat and that gets metabolized in the col in in the body. So you basically shrink the fat in the in the body.

Kevin Folta (11:25.673)
I see, yeah. Well, but there's a lot of fat that's required in the body too. I mean, it serves as helpful padding around kidneys and eyes and things like that, but you know, so so we don't want to get rid of all of it. But so this is just kind of modulating its levels. So now the cool part about this that I really thought was a neat part of the experiment or the the the approach for the therapeutic is that you're using a silencing RNA to shut down act the inhibiting gene.

or actually affect the inhibiting RNA, I would guess. So can you tell us about how that works and what is a stereo pure interfering nucleic acid?

Erik Ingelsson (12:04.344)
Yeah, so we're starting with the stereo pure part, that's really at the foundation of of our company Wave Life Sciences. So that has to do with the how the chemistry rotates in space, simplified. So other companies that are doing these type of oligonucleotides, these are RNA-based medicines, they they are stereo random. So it means every binding could be randomly to the left or right if you want.

And we control it so every molecule gets exactly identical in the 3D space. So that's what it means with the stereo pure. Now getting to this other question, SI, so silencing RNA. The whole idea of that is that to your point, you basically find the RNA that comes from this gene, binds to it, and and basically breaks it down or or like silence it silencing it. And by doing it this way, we can get to this very infrequent dosing.

So we we we already have data supporting that it's at most twice a year, potentially once a year. And you you go and have your basically you go you'll go and have your obesity shot. That would be like the vision here. You get a subcutaneous injection and it acts for up to six or up potentially up to twelve months.

Kevin Folta (13:18.121)
Yeah, and this is a really cool part of it that we'll get to in just a moment, which is pretty exciting. So we're speaking with Dr. Eric Isaacson. He's the CSO of Wave, or no, I'm sorry, I just got to say that again. Jim fixed that. We're speaking with Dr. Eric Ingelson. He's the CSO of Wave Life Sciences. And this is the Talking Biotech podcast. And we'll be back in just a moment. And I go, there's a little blurb here in the middle. Yeah, so far, so good. Good, good, good.

Erik Ingelsson (13:45.74)
Yeah, the stereotypure part became very technical, but it's also quite hard to explain that.

Kevin Folta (13:49.74)
Mm no, it's it's but but is it is it that and this is what so yeah it's in three D space, but you're is it because the RNA is taking a helical form as a oligonucleotide that is in either direction or I guess I'm trying to understand why that is necessary.

Erik Ingelsson (13:52.984)
Three D s it's in the three D space basically.

Erik Ingelsson (14:12.716)
It is basically that an oligonucleotide is a series of you know nucleotides. So if you have nineteen of them, for example, then you have nine two to the power of nineteen versions because every binding can be either left or right. And if that happens randomly, you get a mix of like half a million molecules versus we can have one single molecule. Yeah. Yeah.

Kevin Folta (14:33.279)
I see. All right.

Okay, that makes a lot of sense then. Yeah, that's so it's so it's the the stereopurity of the nucleotides that are going into it that form an oligonucleotide that has a a more predictable structure for yeah okay on the bind okay cool all right so we'll go back into it here so far so good at your answers are right on in terms of depth that really really nice

Erik Ingelsson (14:53.292)
It is it is about each binding of the bindings there, but yeah.

Kevin Folta (15:03.871)
So this is the this is the part I find really intriguing coming up. Here we go. And now we're back on the Talking Biotech podcast. We're speaking with Dr. Eric Engelson. He's the CSO of Wave Life Sciences. And we're talking about the latest technologies in fighting obesity. And before the break, we talked about this approach that that you say are you calling this W V E double O seven? Is that how you're

Erik Ingelsson (15:30.19)
We're usually saying W V E zero zero seven, but yeah. Yeah, no, I know. We've that's a good one. Yeah, that's a good one. We have heard different versions. Yeah. Yeah.

Kevin Folta (15:34.194)
Okay. I kind of had the James Bond thing here, you know, that it was a you know, because it's bonding to the its target. Yeah, well you guys you well you could use that, you know. So this is but this is what's really fun. So it's using an RNA silencing process, and this is where this oligonucleotide, which is RN which is apparently RNA, is finding its target with with this inhibit gene RNA.

And binding to it and igniting the silencing cascade that turns on a process that will have been very well described that now will take out that RNA anytime it occurs, at least for a while. So that's great, but you're said this is a subcutaneous injection. So how do you have take this silencing RNA and specifically get it into liver hepatocytes?

Erik Ingelsson (16:27.874)
Yeah, that is a fascinating thing. So an important innovation here is to put on kind of a sugar molecule on this oligonucleotide, and then it becomes a homing kind of missile if you want, going directly to liver liver cells, because there is a receptor on the liver cells that recognizes this specific sugar, basically. So so it's a very

It's a great innovation and it's a good way of getting a mo one of these oligonucleotides, one of these medicines directly into the right place, which is the liver sauce, where where b the production of inbine is happening.

Kevin Folta (17:06.837)
Yeah, and what is that sugar called? It I see the initials for it, but I what does it break down into? What is it called?

Erik Ingelsson (17:12.716)
Yeah, we it's called Tri Galmax.

Kevin Folta (17:16.139)
Trigalnac, yeah. Okay. So just just 'cause I've I've seen we've talked about glycnacks and things when we talk about signal transduction and so this is a similar kind of sugar moiety that is but it only goes to the liver. Is there any other place that this can end up or is it liver specific?

Erik Ingelsson (17:21.923)
Yeah.

Erik Ingelsson (17:28.876)
Yes.

No, it's like no, it's liver specific and very close to a hundred percent goes to the liver.

Kevin Folta (17:36.627)
they're very cool. So the trial data suggests that this works for a long time. And you had suggested that maybe this was a twice a year treatment, but it's an RNA based therapy. And aren't those supposed to be really temporary?

Erik Ingelsson (17:50.197)
No, I think maybe you're thinking about more vaccines, which is a different thing. So in this case, an sRNA, I would argue that the longer the better, probably. And again, we have data at this point from clinical trials where we so far looked really just seven and a half months in, and at that point it's still suppressed to like the the same level. So we know that it's like at least that long. It and it could be longer. We'll get more data later this year.

so that's why we're saying once to twice, at most twice a year. But there is a potential for once a year dosing as well.

Kevin Folta (18:27.253)
Yeah, I kind of baited that question a little bit because in the discussion is mostly around vaccines and those interventions, but this is probably more persistent because of the RNA silencing s system, right? That you're getting the risk complex and all of this involved, which is actually performing that silencing. And that so the idea here is that the silencing sticks around longer, and that's why it's more effective. Okay.

Erik Ingelsson (18:50.392)
Yeah. Exactly. Yeah, exactly. So so after the injection, the molecule goes to the liver and then gets into the liver cells and then it sits in different compartments of that cell for a very long time, including on the enzymes that are doing the cell inside.

Kevin Folta (19:05.963)
So you did a phase two trial that examined populations with higher BMIs. So people are like 35, 50 and had comorbidities like type two diabetes. And so how did the pharmacod pharmacodynamic easy for me to say? How did the pharmacodynamic responsive activity suppression differ between healthy overweight volunteers and individuals who had more severe metabolic dysfunction?

Erik Ingelsson (19:31.939)
Yeah, so that remains to be seen. So just a small correction is that what we have done so far is the phase one trial. Yeah. So so the data we have at hand today, these are individuals that are otherwise healthy. So they have a you know a slight overweight or mild obesity. The average DMI was around thirty-two, and no other diseases, so no diabetes or anything. And and this was a phase one trial, it was primarily

Kevin Folta (19:38.935)
okay.

Erik Ingelsson (19:58.285)
Designed to look at things like pharmacology, how is it working? Can we decrease the actominal levels as we want to do? And safety. But then we included some measures of body composition as more like exploratory, if you want. And it was really fascinating that all of this was again a phase one study, not really designed for this, and in a low BMI population, that we saw very profound changes in both total fat and visceral fat.

Particular the visceral fat, where we after six months after one single injection saw 15% decrease of the visceral fat. And then alongside with that, the overall fat also around 5% decrease. So so that that was all very encouraging for us. And then to your point, now we're we've just started our phase two A study, which is now in higher BMI individuals with or without diabetes, meaning that

Kevin Folta (20:46.771)
Mm.

Erik Ingelsson (20:53.272)
We're now able to look at the potential in these individuals that have more fat to lose. You could envision that they should have a larger fat loss in that population. And in addition, how it works with diabetes and non-diabetes, and also based on the genetics that we walked through before, you know, we would expect the general effect on a lot of these cardiometabolic risk factors as well. And we're measuring all of that now in the phase two A studies. Well, we're looking at liver fat, we're looking at lipids, we're looking at

H B A one C, which is a measuring diabetics.

Kevin Folta (21:24.467)
Mm-hmm. So in in the phase one trials, did you see a coincident decrease in biomarkers that were associated with visceral fat, even though it was a non overweight population?

Erik Ingelsson (21:37.592)
We didn't we did actually didn't look at that. So we only looked at safety biomarkers, and then and then really just we had body composition with a DEXA scan. that that gives you visceral fat and overall fat and then muscle.

Kevin Folta (21:52.98)
I guess the other is we mentioned earlier that up to 70% of folks who are in GLP one type use that they quit within a year and that this particular therapy is being positioned as a standalone therapy and kind of a post GLP one maintenance therapy. So preclinically, how did this perform in the rebound weight gain that usually follows cessation of GLP GLP one strategies?

Erik Ingelsson (22:21.016)
Yeah, so that's a great question. So what we did in the preclinical studies is what we actually looked at three potential use cases. So the monotherapy, where it actually performed at the same level of weight loss as as semaglutide, which is the most common GLP one. if you added it together with semaglutide, you doubled the effect. So that's the potential combo approach, combination approach. And the third is that we looked what what if you withdraw GLP one?

then they maintained the weight loss. So they were flat in their weight. So so in the in the preclinical models, we have like evidence for all three use cases. And now, as we're going into the next stage of clinical trials in phase two, we're gonna test all three as well. So the 2A we talked about already, that's the monotherapy for the high BMI individuals with and without diabetes. Now, in we're also second half of this year, we're also now starting both the combo trial.

and a maintenance trial as well, where we will give for the combo trial we'll give it in combination with an incretin and for the maintenance where we will have individuals stable on an incretin and then withdraw that and see if they can remain flat in terms of their fat.

Kevin Folta (23:31.593)
This is really neat. So with just to kind of maybe a couple technical questions is how much of the RNA al oligonucleotide do you need to administer with this sugar tag to ignite this response? I mean, how how any idea about how many nanograms or how much goes in?

Erik Ingelsson (23:47.875)
Yeah, so so far in the clinical studies, we have tested four doses, where the first one was seventy five milligram, and that was predicted based on our preclinical data to be subclinical. So we didn't expect a lot of effect there. We actually saw around fifty percent reduction of activity already at that very low dose. But then we went up to the doses where we kind of wanted really to test, and that was two hundred forty milligrams, four hundred milligrams, and six hundred milligrams. So three different dose levels.

And what it turns out that it is that I already the 240, so the lowest of those three kind of clinically predicted doses, we saw a very profound effect. So the the numbers that I cited with like you know around five percent of total fat loss, around fifteen percent of visceral fat loss, that's six months after that single lower dose, the two hundred and forty milligrams. So so so and that's also where we at this point have seen over seven months of durability with that low dose. Now we we still

will later this year look at remaining data and learn more about like dosing and pharmacology as we go into the phase two trials now. But we have already started the phase two A and that will test the two hundred and forty and the four hundred milligram doses.

Kevin Folta (25:01.237)
Yeah, it's I was saying nanograms 'cause I thought that this might be a very small amount that's added. You're talking about, you know, st two yeah, you're talking about milligrams, which is, you know, you're getting two hundred forty milligrams or a quarter of a gram. You know, it's pretty seems like a pretty good amount. Is that just because of the adverse pharmacological environment of the body that wants to turn over RNA that this that only a subset of what you administer actually gets to the liver?

Erik Ingelsson (25:07.616)
Milligrams, yeah. Yes.

Erik Ingelsson (25:26.382)
no the no the absolute majority comes to the liver, but it's more about the durability and you want to get to that once a year dosing. And just for context, there is a drug already on the market for lowering LDL cholesterol through a mechanism called called PCSK nine. And this is a drug call called enclycerin, which is given twice a year and that's two hundred and eighty four milligrams. So it's really in in that same range. And and an additional point that is also relevant here is that it's still a one single injection.

So you don't need to take several shots, it's one subcutaneous injection.

Kevin Folta (26:00.79)
Yeah, I really want to talk to them on the podcast too, because that's a really neat one, too. But our in RNAI in general, it's never as rarely used as a therapeutic. And there's a few examples where we can find that. but this particular one, it really represents a shift towards treating mass market chronic conditions with oligonucleotides. So it's super cool. So, what's the biggest problem or the biggest hurdle in manufacturing or delivery or other clinical hurdles that

Erik Ingelsson (26:17.314)
Yeah. Yes.

Kevin Folta (26:27.995)
you have to overcome technically in order to make an annual silencing RNA injection really the standard of of care for obesity.

Erik Ingelsson (26:37.186)
Yeah, so in in theory, there is nothing like these are small molecules. It's chemistry molecules. So it's it's if you compare with a lot of like, you know, gene therapies, cell therapies, even biologics, these are in in many ways much simpler processes. It's it's really enzymatic processes for creating chemistry chemical molecules. It's it's not very different in that sense, I would argue. Now, to your point, it is it has been kind of a movement fr this is traditionally been more for rare disease.

And it's now moving more and more into common disease. And and this this class within a BNE, that's like one example. I did mention the one that is launched that is for also for mass markets for LDL cholesterol, in the enclycerin drug, but there are additional additional molecules coming out now in late stage trials and also being launched now for common disease. So it's I think it's a big wave, pardon the pun, of new

this new modality that is kind of following the traditional modalities of small molecules and biologics. Now this is a third really major modality that's starting to be very common, both for rare and common disease.

Kevin Folta (27:49.398)
Yeah, this is all really cool stuff. I I you know I've been I've been studying molecular biology since I was a little kid and I just love to see these innovative approaches. So why you don't have a crystal ball, I totally get that. But what's the timeline like on these kinds of inhibitors if everything goes as planned?

Erik Ingelsson (28:07.852)
Yeah, so I think generally on on these type of s RNAs, they're really kind of coming in into fashion. I think most several reasons for it. One is the specificity, very high specificity. And the second one is durability. You can get very long durability to this point. Like for our in a B SRNA specifically, we're now starting the two A study. we're still a few years out. We haven't guided exactly when we plan to kind of

finished we need to go through both two and phase three studies before we can get it approved. But you know, it's it's it's not that far out, but you know, it's it's a still a couple of years to go.

Kevin Folta (28:47.143)
super cool. Is there anything else in the pipeline at wave life sciences that you could kind of give us a little bit of a hint as to other things that may follow the same kind of approach?

Erik Ingelsson (28:58.37)
Yeah, so we have several earlier SRNA approaches. We haven't disclosed those targets yet, and and the whole, you know, competition has been heating up recently and we t try to keep the target names a little bit close to our vest for that reason. but what I would mention is that we have other clinical programs, and we are traditionally

Agnostic in terms of different modalities within the oligonucleotide space. And now we have been doubling down on sRNA that we talked about today. We were also the first ever to do RNA editing, which is another very cool approach. So in that case, you're doing an editing of a specific variant or mutated base and reverting it back to wild type. So there we have two programs. One is already in clinic in phase two, and the other one is going into clinic this year. And the first one is

For rare disease, alpha one anthrocypsin deficiency, so it's a liver lung disease where we can correct it back to the wild type. And we have a lot of very very exciting data there already from Clinic. And the next one is going into a specific genetic form of liver disease, that are, you know, nine million individuals across US and Europe in total, and it drives both MASH and other liver diseases.

Kevin Folta (30:17.587)
Very cool. So if people want to learn more about Wave Life Sciences, where do they find you on a website or in social media?

Erik Ingelsson (30:25.314)
Both. so wave life sciences dot com and we're also both on you know Twitter and LinkedIn and different social media places.

Kevin Folta (30:33.195)
So just look for Wave Life Sciences. very cool. Well, this is really super exciting stuff from a technical side, but also for the potential it holds to solve the problem of obesity, not just from the input side like GLP1s, but now getting rid of what's there. And it seems like a real good complement, if not an extension of the modern therapy. So, Dr. Eric Ingelson, thank you so much for joining me today. This is super exciting.

Erik Ingelsson (30:35.864)
Yes, correct.

Kevin Folta (30:59.315)
And I hope that you'll join me again after phase three and this thing gets accepted. So thank you very much.

Erik Ingelsson (31:05.262)
Thank you so much for the great discussion.

Kevin Folta (31:07.423)
Yeah, this is a lot of fun. So when we start thinking about the new innovations, you can see how this could have a profound role in the issues of obesity, which have which have cascading effects throughout everything, from how much it costs to get a plane ticket to the the the the stock market around coke and Pepsi. I mean, this this stuff has impacts. So keep an eye on these technologies, and most of all, think of ways in which these kinds of targeted silencing RNAs may find new roles in other places.

Erik Ingelsson (31:27.512)
Yes.

Kevin Folta (31:36.811)
From things like obesity, but certainly cancers and other diseases are on the menu. And in things like sickle cell or or even even cystic fibrosis, lots of places where these things may eventually have some sort of application. So those are more RNA editing. Jim, let me fix that to fix that last sentence. let's see. It's very exciting to see how these kinds of RNA silencing technologies through oligonucleotides.

may play other roles in other diseases and other issues like cancer, all the way through other rare diseases. So this is the Talking Biotech podcast, and we'll talk to you again next week. All right. I had to redo my ending there. I screwed up. I got RNA editing mixed up with my