340 Stopping Bleeding with Algal-Based Polymers
===

Kevin Folta: [00:00:00] Hello everybody. And welcome to this. Week's talking biotech podcast. This week, we're going to talk about an issue with bleeding or even more importantly, stopping bleeding. Now bleeding is an interesting process because as blood moves, we have to walk a very fine line between this issue of blood that flows and blood.

Coagulates or glutamates or or forms of thrombus or the platelets grabbing and a, an elaborate cascade of events occurs that allows bleeding to stop. And you can see how this is pivotal to existence that if you lose the blood, you can anymore, you know, move oxygen throughout the body at the same time.

If you create clots too. You can have other types of problems as well, such as heart attack stroke or other types of thrombosis. So there's this very fine line that the body has to walk in an elaborate feedback cascade between clotting and not clotting. [00:01:00] At the same time, there's been an issue with how do you treat a catastrophic bleeding event or, or someone who's experiencing significant blood?

Yeah. And in the past, there've been certain tools to do it, but new tools exist. Now, today, we're speaking with Joe Landolina, he's the co-founder and CEO of Cress Alon, and they're coming to us with new ideas about how to stop bleeding. So welcome to the podcast, Joe. Well, 

Joe Landolina: Kevin, thank you so much for that.

Kevin Folta: Yeah, I really appreciate it. This is an interesting idea because of many facets, including that these solutions are plant-based. So let's talk about first, what the problem really is. I did that little bit of an intro there about bleeding and clotting and things, but then I mostly get that. So, 

Joe Landolina: so you did, but the biggest issue in stopping bleeding, especially traumatic or excessive hemorrhage is that the body is such a dynamic system.

And as an engineer myself, when we look to design [00:02:00] products for the system, you can have the best product in the world the best clotting agent in the world. But if that blood clot is getting washed away and is flowing downstream, it does nothing for the injury itself. So you need to design technologies that not only allow the body.

Form of blood clot. I've been also stay in place for the duration of treatment. And that really is the key and what we do with cross along 

Kevin Folta: well, let's start by defining the problem. How frequent are issues of traumatic blood loss and where do we most commonly see that? 

Joe Landolina: Sure. So bleeding occurred just about everywhere and in animal health, which is one of the first markets that we entered with our, with our product that are gel.

There are over 3 million bleeds every single year in animal health, in the U S alone that require. To to stop that bleed. And this ranges from everything from tiny dental extractions, all the way up to massive hemorrhage, arterial or venous bleeding. And if we look at a statistic from the U S military we can see that [00:03:00] 91% of battlefield deaths are due to what we call preventable hemorrhage.

And then that means that if only there were a product to stop bleeding more efficiently we, we can make a strong difference. So not only in the operating room, but also in the field in point of. 

Kevin Folta: Well, let's hit that number again. You said 91% of battlefield injuries. 

Joe Landolina: Exactly. So, so 91% of what we what they class is preventable deaths come from or due to hemorrhage.

Kevin Folta: Well, and do you have any statistics or any general idea of how much of that applies to other types of accidents? Like automobile accidents, for instance like that you have so much bleeding on site that you just can't treat any of the other. 

Joe Landolina: Exactly. I mean, that statistic applies only to battlefield injuries.

And so if we think about all of the other categories of bleeding, especially traumatic bleeding from motor vehicle accidents to to violent crime, that results in things like gunshot wounds, stab wounds. That those numbers are staggering. [00:04:00] And on top of that, if we think about the average time of response, especially in the United States, the average time of response is minutes.

Sometimes over 10 minutes to get an ambulance or a medic to the point of care where a patient is experiencing bleeding. So by the time that you, as a medic get to a patient or to a casualty time is of the essence. So every single second that you can save with a product that can stop bleeding faster. We'll we'll help save that.

Patient's. 

Kevin Folta: Yeah. I don't know that people really appreciate how fast blood can move out of a body. And I know that I've seen examples of arterial bleeding before where the pressure in the artery system, a arterial system from the heart is so high. I mean, the blood, the blood literally moves meters and it, and just, you know, a pint of blood on the ground.

It looks like a lot. I mean, you really, really lose. Blood fast in some instances. And so what are the, really the, the current suite of remedies to approach this [00:05:00] kind of catastrophic or traumatic? 

Joe Landolina: Sure. So at the very top end of the of the, the chain for products like this especially traumatic products the vast majority work by using some sort of impregnated gauze, as you take a strain of gauze, usually three meters.

And you and pregnant with some sort of clotting agent and back in the day that used to be zeolite which was effectively a solid state acid that causes a rapid coagulation. And, and today the. Technology is mainly Kaylyn which is effectively a clay. And what that does is aggregate and activates platelets.

And that with compression will control traumatic bleeding in somewhere around five to seven minutes. Ideally. However, the vast majority of, of patients that have been left to bleed for some time experience. Trauma induced. Coagulopathy meaning that as you bleed out, your blood factors bleed out first.

So if you have a product that's reliant on the clotting [00:06:00] cascade on SAR, by the time that you get to that patient, that clouding cascade has been diminished so that there is a strong benefit to having a product that works primarily in a mechanical fashion. Whereas in today, most of the products.

The mechanical or the mechanical action that comes is from pressures from the medic, applying their own pressure to the bleed and everything else is. 

Kevin Folta: Yeah, it seems that even back when I would take first ad, you know, pressure was the main thing that you would do. I've been on scenes of automobile wrecks, first person on where I've actually had to do it.

And that's kind of scary, cause you never know sometimes, you know, the blood these days, if you know, this was actually, that was back in the nineties back when everyone was really worried about HIV transmission through blood, we didn't know exactly how it was transmitted. And so it was always a concern, but what about something like where you had severe arterial bleeding, where they would say apply a tourniquet where you're basically life or limb kind of situation are products like this?

Like, you know, what, what you're talking about and we'll [00:07:00] get to your product in a second. Are they really kind of working towards that level of blood loss? 

Joe Landolina: So it depends. And if you look at the, if you look at the medic or, or the, the war fighter of today there, there is a a committee called teachers triple C, which would provide SLPs for treatments of various types of injuries, including hemorrhage.

And in most the case is the easiest form of controlling, bleeding on a limb is tourniquet application. So I I've, I've been through T triple C training myself. And the first thing that gets hammered into your mind is that if you can put a tourniquet on it and put the tourniquet on it, because that will be far easier than anything that, that works through through pressure or through chemical action.

Because especially if you're a medic that there was a saying that I came across once, which is a one casually on a battlefield leads to four more casualties because you require medical staff to both evacuate and treat the cat. And the more that you can do to keep that medic hands-free and [00:08:00] focused on the job at hand, the better.

So, so tourniquets definitely have their, their spot in the portfolio where things start to break down, or when you have junctional hemorrhage or, or hemorrhage in an area where you cannot apply a tourniquet. 

Kevin Folta: No, I, I totally get it. That's what it was really interesting about learning about this technology is that this is a.

Matrix that ceases blood flow within seconds, but it's a plant-based product and being a plant biologist, it makes me wonder, you know, what exactly are you using from a plant that is translating to stopping hemorrhaging? 

Joe Landolina: Definitely. So our technology is based on two polysaccharides that are derived from the cell wall of algae.

And what I'd like to take a step back on is just look at the material as a whole. And really what we're doing is we're creating a material that works as a really great. Even in the face of an incredibly wet field. So meaning even if we have a field that's completely covered in blood with pumping [00:09:00] arterial hemorrhage, we want to do is design a set of material properties that can still be adhesive in the situation that can be just viscous enough or just heavy enough that if it's placed in an area of high pressure flow, it doesn't get blown away, but just flow.

That it can flow into all the nooks and crannies of the wound. And what we do is we do that by creating a composite material of two well-known and biocompatible polysaccharides, and we created a viscous gel out of it, which is if you've seen videos of our technology, it's effectively the consistency of hummus, where it's a highly viscous paste that can get topically deployed.

And once it goes on in two and a half seconds or less, you can create. Immediate hemostasis, but more importantly, it allows the body to create a fiber and pattern underneath. So if you remove that material, if you remove the gel, what you're left with is an endogenous fibrin patch, meaning a five from patch that's been created only of the body's own materials that is remained behind and [00:10:00] unlike other materials or products that are porous, the clot that forms does not get incorporated within our materials.

So if you take off the gel, the cloth stays behind intact. 

Kevin Folta: Okay. That was my other big question. But now you're gonna have to pardon my ignorance a little bit here and kind of hang with me here. I've had injuries before that have been extremely have had some bleeding and maybe had some compounds in them that were actually limiting the ability of the blood to clot.

And I was in a remote area and I used a tube of superglue to close it up and it worked. It sounds like you're in a similar vein that you're using. You know, polysaccharide compound something that is that's working as an adhesive, but here's the, here's the part that I don't get this compound kind of comes as a piece that's in a syringe that you apply to the wound or to whatever, but why does it not.

Work as an adhesive inside the tube. You see what I'm saying? It's not like a two-party proxy that you put together that a chemical [00:11:00] reaction occurs or is it some sort of reaction that's happening with oxygen or with the body or what makes it form a patch for the wound, you know, on the wound itself and maybe not in other countries?

Joe Landolina: Perfect. So it's really a two-stage response. So the first stage is fix a Tropic, but it which I'll explain it in a second. And the second stage is ionic, which we'll also explore. Explain. So thanks to Tropic fluids like cornstarch and water are those that when you float out of the syringe, the material properties change as a function of movement of this fluid.

So that means that the gel, as you deployed out of the syringe will thin considerably. And when it hits the wound, it'll immediately. Recoil and thicken up. And especially if you apply pressure to it, it becomes thicker and thicker as you apply that pressure. And that allows it to in the syringe be a a paste or, or, or a flowable gel.

And then as you deploy it, it thins down and then thickens up to actually grab onto the wound and [00:12:00] help along with that, that adhesive. Actually the second is through ionic action and ion transfer between the gel and the tissue itself will allow the gels function to be only temporary. And what that means is that as time goes on from the blood, from the surrounding to.

I also in the body will transfer into the gel and that will reduce the adhesive profile because what you want in an injury like this is you want the body to be able to create its own cloth. The worst thing that you can do in a massive hemorrhage is to have. Gel itself, which is a massive bowl, is connected to the fiber and patch because as the patient breeds as the patient moves, you're very likely to have the gel, if it's stuck to fiber and pull that fiber off.

And that's what we see with a lot of other ways that we treat bleeds. And that's one of the reasons why with siren or accurately, or with a, with a superglue. Why it doesn't work on very large hemorrhage because is activated by water. And if you put this into a if you put this [00:13:00] into a large pool of blood, it will immediately all react and it doesn't do anything to the, to the tissue below it.

And when it does it's irreversible or, or at the very least very difficult to remove, and what we want is a material that can be dynamic that can help the body do what it does best, and then be easily removable at the end, so that you're not destroying tissue or causing the CRO. 

Kevin Folta: And I guess a lot of people may be thinking there's been other ways that we see used around the house, you know, for instance you know cornstarch, you know, when you have a dog that has an injury, like a toenail or something, they tell you to put cornstarch on it, this is the same kind of thing, like activating some sort of polysaccharides that are present in plant stuff that that formed this, or are these specialized polysaccharides from So it's 

Joe Landolina: a little bit of both actually.

And that's one of the benefits where these materials have been used in the industry before. And as a result, their toxicology is, are well understood. Their pathways are one of the just stood and that allows us to have much more confidence in this material because it's not [00:14:00] entirely. And that means that we see things like we see in other plant-based hemostatis where we see factor 12 activation.

We see things like platelet aggregation, and we know what they will do when they get put in contact with the body. But on the other hand, these materials in order to form the right material properties or the rheological properties that allow us to do what we do, we have to purify them and select them.

In a, in a very distinct and informally proprietary way that allows this material to stand up the way that it does to high pressure. So if you were to take our two polymers and buy them off of Sigma or off of Amazon and mix them together, even in the exact same way that we have, you would get a gel that looks like ours, but that would not stop bleeding.

Kevin Folta: Okay. Then they'll see that it helps a lot because I'm trying to pick up. You know how this can work. It seems almost like a little bit of magic it, especially when you start talking about, you know, factor 12 and all of the other [00:15:00] factors. And I won't bore the audience to death with how clotting work, but it's, it's a real, very careful orchestration.

So how does this stuff. In a it's a, so does it work in a mechanical way that does not trigger other types of clotting? So in other words, you didn't know indiscriminate clotting that could lead to any other thrombogenic events, like maybe, you know, heart attack or. 

Joe Landolina: Sure. So one of the benefits of this material is it's hyperlocalized response.

Meaning when you put this into tissue, you will only see fiber production right. At the barrier, right. At the surface of the gel. And that, that layer is typically so thin that, that it does not progress into the blood vessel. And because our product is a single bolus and it doesn't break up, it means that you're, at the very least, it doesn't increase the risk of thromboembolism to the.

And then. Beyond that the material properties that we have are primarily mechanical, which is [00:16:00] very important. So we had in our animal health product that our gel, a few weeks ago, we had a patient which was a, an exotic cat that had ingested rodenticide. And that, and rodenticide works by completely reducing the ability of the body to produce a cloth.

So this patient was effectively bleeding. And and our product was still able to be efficacious in that scenario. And while you can't remove the product, leaving behind an indogenous clot, if you leave it in place, it, it shows that that mechanical action is primary to the, to the mode of action of. 

Kevin Folta: Well, this is really fascinating stuff and really solves an important problem.

So we're speaking with Joe Landolina, he's the CEO and co-founder of crest salon, and they're coming up with new types of algal based strategies to be able to stop bleeding, which is a really important process to be able to stop sometimes. So this is collaborative talking about a tech podcast and we'll be back in just.[00:17:00] 

And now we're back on the talking biotech podcast by collaborative. We're speaking with Joe Landolina, he's the CEO and co-founder of Cresa Alon. And we're talking about a product that they're, they've created. That allows bleeding to stop in seconds, which can revolutionize a lot of immediate blood associated traumatic events.

And before the break, we were talking about the mechanism and how this was working, but I have maybe some big picture application questions. Like, is this the kind of thing that you can use on an internal bleed as well as, you know, say an external wound, like maybe some sort of. In aortic aneurysm, something like that, where if you could get the patient open, that you could stop that faster.

Joe Landolina: Exactly. And that that's one of our bread and butter indications is, is internal. And we were talking earlier before the break about superglue and how superglue can work on external bleeds. If you try to use something like that internally, you would create. Damaged the tissue and with a product like [00:18:00] this, there's a strong benefit to being able to stop a hepatic injury.

A plant-based biocompatible matrix that does not cause tissue necrosis and can resorb into the body. And again, that's another benefit of a plant-based material that these plant-based materials will break down by hydrolysis over time so that they can be left in the abdomen. And what, 

Kevin Folta: what kind of polysaccharides are these?

I know you mentioned this earlier that they're algal derived, but what kind of molecules are they and why are they so. 

Joe Landolina: So as a plant based or as a plant biologist, you're going to laugh because the chemical names are so common. I remember I use these as a kid working in a lab. They are, we use a variant of sodium alginate and we use a variant that that's ankle derived of.

And these, these materials again and the, the trick here is the way that we purify them. But from a chemical name and from a chemical species, these are super simple and common materials that [00:19:00] we're able to blend together in the way. But like I said, if you took any old alginate from Sigma, from Amazon, or you took any old cotton from Sigma for Amazon, then you mix them together.

You wouldn't get something that worked. The trick here is the way we mix those. 

Kevin Folta: It's really fascinating stuff, kind of repurposing what nature already made to solve problems in, in all kinds and especially to be able to come up with a solution for a problem and fungal fungi more than anything else, I guess.

But let's talk a little bit more about you know, as application, a lot of discussion around bandages and band-aids that kind of thing that they've said, well, we're going to start to impregnate these. Other compounds like antibiotics or even growth hormone to speed the healing of the wound. Is that kind of on the radar with this kind of.

Joe Landolina: And so while that's not something we have an indication for right now, it definitely, at least the engineer in me sees no issue with being [00:20:00] able to impregnate this matrix with anything and being able to give it a variable profile meaning that if you want something to a loop immediately or.

Over the course of a few weeks, that's doable. And with the way that this matrix is set up so looking at the delivery of antibiotics or other therapeutics is something that's definitely on our radar. 

Kevin Folta: You mentioned before that this is being used in veterinary applications. And can you give us an idea of what some of the more common usages are?

And are there any particular stories you've heard of where this really made the difference in saving an animal's. 

Joe Landolina: Yeah, of course. So we, and what's interesting, is it some of the bleeds that you see in in animal health may not seem as traumatic or, or as hard to stop, but like dentistry, as an example, if you're a dog.

Hold gauze on your own tooth for 25 minutes after waking up from from a procedure in order to stop the bleeding. So [00:21:00] that means that they have to keep an animal under anesthesia increasing the risk of the patient and increasing the cost and clocking up in our table while they're waiting for dental bleeds to stop.

So dentistry is about 10% of the bleeds in the entire animal health market. And that's something we're really, it's his bread and butter for us being able to put this into a into a tooth socket and. About 15 seconds later, that also helps in complicated surgeries where it makes it easy. If you break a root to see where the root is and where Jawbone starts, so that you're not drilling into bone, you're drilling into tooth.

And it really allows a surgeon in this space to have even in something that's a relatively minor bleed. Well on one hand to be able to see more patients in a single day, and to have more confidence in their own technique to be able to not injure the patient and improve outcomes. We've also seen this product be used in amputations.

We've seen this product be used in your nucleation, which, which are the loss of the eye. And the eye is [00:22:00] served by both an artery and vein that can retract into the skull. And those bleeds can be. The same is true with space procedures. The ovarian pedicle is incredibly fryable tissue, meaning that it can break under pressure.

And if that pedicle re retract in to into tissue, those bleeds can be life-threatening and no one expects to see. There are animal die on the, on the table when they go in for a simple procedure like that. But a product like this gives a lot more confidence to the to the surgeon. And then we've also seen more complex surgeries where I was lucky enough to be able to observe a number of cases in oncology where tumors in order to gain more oxygen, to help them grow faster, they finished rate their capillaries meaning that they make the capillaries.

I bit more oxygen flows into the surrounding tissue. So if you cut through cancerous tissue, it bleeds and it bleeds significantly. And what you don't want to do is use a lot of electric cautery because you're causing tissue necrosis. So having a product that can control that type of bleed, especially if [00:23:00] there's a tumor around an artery or a major vein that gives a lot more confidence to the surgeon, reduces operating times, which saves.

Kevin Folta: That's really good. I, is this something that could have a consumer animal application? Sometime soon. And the reason I ask is, you know, we, I live on a farm and we have a lot of animals that because of either an accident or maybe a attack of a predator. That you get bleeding events that you have to stop and have to treat.

And, you know, emergency vets are extremely expensive and you usually have to put an animal down rather than do that. Plus it usually happens at a super inconvenient time and it's far away, you know, most people who are on farms or are minutes to hours away from a veterinary facility. So is, is there any room for this kind of thing for a home-based applicant?

Joe Landolina: So a consumer product is definitely well on our radar, both for animal use as well as for, [00:24:00] for human use. Eventually. However, the product that we have currently on the market was really designed by packaging and by training for use by surgeons. And so it, it will not be immediate that we release a product like this.

But I, I definitely see the. 

Kevin Folta: Yeah, I do too. I wish we had some here. Last week, we had a goose who got his head caught it's mating season and they do dumb things and ended up getting caught on the neck and you get some bleeding and it's very difficult to control with a, you know, a medicine cabinet solutions.

But what about humans? So you mentioned all this for veterinary application seems like, you know, human trauma is going to be the big one, especially military or in first responders. When is this expected to be available for that application? 

Joe Landolina: Sure. So w we're we're in a really exciting time right now across along, because we filed in November of last year for our first human use and with the FDA.

So we're expecting that the FDA should clear that product for use in human [00:25:00] sometime this year. And that means that we'll be able to continue our mission of saving lives by expanding to human. 

Kevin Folta: Does having it be a natural compound or a compound at least derived from algae change, the FDA's evaluation process, or, you know, you're not testing some sort of synthetic analog of some other kind of drug you're using something that is already made.

And, you know, does that change the dynamic of this? 

Joe Landolina: So while I can't speak for the FDA, it definitely makes the regulatory process simpler from our perspective, because we have two materials that have been used before on the market. And that lends itself incredibly well to the five, 10 K's product device program.

Meaning that if you can show that there is technology that has already had an established safety and efficacy profile, it, it shortens the path to market. And that's something that has been very. 

Kevin Folta: Well, what are the next level spinoff events of this kind of technology? Are there other [00:26:00] applications that we haven't discussed here that might be on your radar?

So from, from 

Joe Landolina: our perspective we are, I'm working right now for a general external hemostatic indication. From there, we'll go into trauma youth looking at the looking at military and emergency room. Even things like dentistry and we're on the human side of being able to stop a molar from bleeding in two seconds, as opposed to waiting all day, especially if you're a patient on blood thinners to to get that tooth under control could be a game changer, even if it may not be life-threatening bleeding.

And then looking at this as a, as a surgical hemostatic device it is. Something that we're working to bring to market as well. But then beyond that, like we mentioned and discussed earlier in this in this conversation is taking the technology, which having a biocompatible plant-based matrix that stays in place and doesn't go away until you want it to is helpful for other applications.

So things. Potentially branching out into drug delivery or [00:27:00] therapeutic delivery tissue, regeneration and, and so on are well within the scope of what this technology can. Yeah, I love 

Kevin Folta: the dental application. I lost a tooth a couple of years ago in an accident and, and you know, it's amazing how much they bleed when they come out.

Joe Landolina: But, and it's it's something where it's, it's amazing. I also had the opportunity to share. I have a veterinary dental practitioner and just seeing and how much blood there actually is and how difficult it is to see what you're doing and having something that I can clean up the field and help the patient recover sooner is a, is a game changer.

Truly 

Kevin Folta: interesting that I didn't even occur to the sin occurred to me earlier that one of the huge applications must be in people with PR with genetic clotting deficiencies. So folks with different types of hemophilia or factor five things like this, are there opportunities to treat them in ways that would maybe be like, 

Joe Landolina: Exactly.

And again, that is the [00:28:00] benefit of having a device that works primarily by mechanical action. And while you can't pull the product off immediately, you have to wait for that clock to form naturally. It allows the same type of have confidence in hemostasis, whether you have a clouding compromised patient or, or a healthy.

Kevin Folta: No, I, I love it. So if anyone wanted to know more about, about the product or its progress through the approval process, where would they look? 

Joe Landolina: So I would direct anyone who's interested to our website, which is w. W dot Cress, alon.com, C R E S I L O n.com. 

Kevin Folta: And do you have a account on Twitter or social media?

So 

Joe Landolina: we, we do we have Instagram, which is at crest salon. We have Instagram at Vedder gel underscore us. We also have a Facebook page under the same LinkedIn page and a Twitter. 

Kevin Folta: Yeah, I think I'll follow because I think it's cool. I think you guys could put up a success stories from veterinary [00:29:00] applications and win a few hearts and minds.

So thank you very much for joining me today. We were speaking with Joe Landolina. He's the co-founder and CEO of crest salon. And thank you for what you do and looking forward to exciting products in the future. 

Joe Landolina: Well, thank you very much, Kevin. It was a pleasure to talk to you. 

Kevin Folta: And as always, thank you for listening to the talking biotech podcast.

It's not always DNA that does the magic. Sometimes other bio-molecules can have important roles in application and solving important human problems. So this is the talking biotech podcast, and we'll talk to you again next week.