TTT012 Making injections effortless - Conor Cullinane - Pirouette Medical

12:29AM Jan 14, 2021

Speakers:

Jonathan

Forrest Meyen

Announcer

Conor Cullinane

Keywords:

device

injection

epinephrine

patient

drug

technology

space

perform

process

talking

design

needle

affordability

injection site

portability

epipen

allergen

easy

people

piece

It's very intimidating, very anxiety-driving, very fear-driving, and all of these things add up to where – when we were looking at our study of patients that were just using trainer devices in a calm, clinical setting – 15% of these individuals refused to actually try and perform an injection.

Welcome to Tough Tech Today with Meyen and Miller. This is the premiere show featuring trailblazers who are building technologies today to solve tomorrow's toughest challenges.

Welcome to Tough Tech Today! We have a special guest, Conor Cullinane. Conor is the CEO of Pirouette Medical, a company that is making a revolutionary new auto injector device. Hi, Conor, welcome to the show.

Hey, Forrest, thank you for having me. Thank you, Jonathan. It's great to see both of you and get to share a little bit about my journey.

So Pirouette Medical, what kind of company is that? Do you make some sort of medical ballet slippers? Or what is your company about? Why did you pick that name?

Yeah, so that's a great question. One we often get, I think a lot of people are always intrigued by the name - we found it to be very helpful. As far as its origins and what the company does, we are a medical device manufacturer and design company. So we found a need in the medical space, we developed a device to meet that need. We're currently taking that design to practice manufacturing, and then through FDA approval and onto the market. That's the overall process of what we've set out to do as a company. Why Pirouette Medical? It is based on the actual dance move a little bit. So when you do a pirouette, it's a revolution, it's a spin. We like to play on that a little bit because of the the design of our device, as well as because of the connotation that it has with that revolution. We saw what we were doing as very different than what had been done before. Rather than saying we're revolutionising that space, we like to say that we're making a pirouette in that space. I really liked the name and we've definitely had a great time, leading with that and continuing to keep that thought process as we look at different technologies, or different applications of our technology, and really focus on continuing to make that revolution or that pirouette, in the medical technology space.

Thank you for explaining that. That's a nice tie-in in terms of the way that the device works and the philosophy that you have for the company. For our listeners and our viewers, could you elaborate on the problem area that you had identified - you mentioned that you found this opportunity in the medical space. Could you elaborate on what that is, why it's important? Why we should care?

Yeah, you bet. It was at a period of time when I was completing my PhD, and essentially, came across a couple of news articles over a very short period of time. So, one day I read an article about a child who was exposed to a life threatening allergen - I think the the first article I had read was a exposure to a peanut at a school cafeteria - the child unfortunately didn't receive a life saving dose of epinephrine in time, and unfortunately passed away. So it's a very sad story and something that popped up and so my PhD focus was medical engineering and medical physics, and so, sort of a space I was already really interested in and it definitely struck a chord. A couple of days go by, and I all of a sudden see an order another article. And it's another child who was exposed to an allergen - in this case a bee sting out playing in a field at a park - and didn't receive their life saving dose of epinephrine in time and unfortunately passed away. One of those articles, you see that and it's, whoa, something is wrong here. And then you see two of those in a matter of of days, - this was all within a week - and it's like, okay, let's take a look here and see what's actually going on. It's tough to hear it, that it's actually still happening. And so we started to dive into that aspect of a medical device that really didn't seem to be solving the problem that it was there to solve. And, our thought process was, well, why didn't these children receive their life saving dose in time? It's very evident how they became exposed to an allergen, you're never going to be able to escape those 100%. You and your family and your parents or whoever can do everything they can to protect you from exposure, but oftentimes, those exposures happen at a time when you have no idea and no expectation. And so our initial thought process was, well, hey, this is a portability issue. And so we looked at existing injection devices, and we said, they're too big, they're too bulky, they're too hard for a 12 year old kid to carry around and try and remember it when they go anywhere, and that's where we started.

Is injection, the only way to mitigate these effects, once the allergies are occurs - the reaction?

Once the allergy occurs, the current emergency treatment is an intramuscular injection of epinephrine. There are other treatments on the horizon, there are other companies looking at ways in which we can have other emergency treatments that could potentially mitigate these issues. But currently, that's the only way we have to save a life in this scenario. And you hope that when you're exposed, you don't have a severe enough allergic reaction, that there's going to be a life threatening issue, but unfortunately, that's not always the case for everybody, and oftentimes, the individuals who have these reactions that are life threatening, those situations are extremely rapid, as well. After exposure, some of these individuals can actually pass away within five minutes, if they don't receive that aboard of the life saving dose in time. So it's, it's extremely scary, and you can start to think about, well what needs to happen during that period. Let's say you've got your device in a backpack, or it's in the glove box, or your car, or wherever it is, you first have to find the device, then you have to get it to the individual that needs it. So if it's yourself, you know, you've got to find it and, then be able to use it on yourself. If it's a parent with a child, they need to be able to dig through that backpack and grab it or run back to the car and grab it, bring it back to that child and then use it and five minutes is not a long time. It's a very scary scenario and one of the big things that we really started to figure out, as we went out and talk to patients and potential users who rely on these devices to save their life is a huge part of their life is just filled with constant fear. Because if you're allergic to a bee sting, or if you're allergic to a peanut, you don't know when you're going to come into contact with one of these things and so you could be out mowing the lawn - I have a really good friend who is severely allergic to bee stings, they're in one of these life threatening manners, just like we were talking about. And he has been out mowing the lawn before, was stung by a bee and, barely survived. This is an individual who actually did perform an injection on himself, actually currently carries an EpiPen on a holster on his on his belt. And so if you're thinking about - this is an adult, and they're constantly in fear of a situation where they might need a life saving dose so much to the extent that they need this on their belt, no matter what they're doing wherever they go outside, because a bee could get them at any point. And then you think is a child going to have that same discipline to make sure they have that and that's where it starts to get really scary and sort of dangerous as you look across, not everybody has that discipline, and if he didn't have it with him that close it would have been fatal. So it's extremely scary for these individuals.

This problem has been around then since humans have had severe allergies and so what gap did you see to be able to make a novel medical device for this - patents were granted and pending - and then wrapping a company around it. Because that's a whole different thing of here's a problem, but then coming down the path of finding a way to be reimbursed for this kind of medical engineering that you're doing.

Exactly, yeah. So when we started to initially look at this landscape, and the current devices that were there, you can kind of trace it back all the way to when injection started, the first types of devices which were really syringe like and then you kind of have the full blown syringe safety syringes, those sorts of things. And they developed over time to the point whereproviding an intramuscular injection is something routine that can easily be done, but this is really healthcare provider dependent. You're receiving an injection by somebody who has the training to provide that injection. You're dealing with a needle, you're dealing with a syringe, you're dealing with the drug, you have to get all three of those components together you have to get the drug at the correct volume, the correct dose. And then all of that has to happen in one of these high stress, blood pumping environments where somebody's life is on the line. And so you come from that preliminary world where it really works great for a lot of the early injections, but in an emergency use scenario, it really wasn't cutting it. And so then, in the 70s, there was the development of the auto injector. This essentially was the automation of the use of a syringe, so that's sort of kind of how this technology came to be. Right? You have all this fear, and this anxiety associated with overcoming the use of existing technology that was such a barrier, that at home delivery of these injections was especially on a mass scale - we're talking about today, 10 million devices a year or more - was prohibitive, right. And so then the auto injector came around, and it was essentially, like I said, that automation of that injection. You really can think of those technologies as just that. You basically have inside of those technologies, the needle, the glass vial or syringe that's actually holding the drug, a plunger, the stem. When I say that's automated, it's basically got a big spring that sits on top, and when you go to perform the injection, you're basically releasing that spring, the spring pushes that needle down, it pushes the plunger down, forces the drug out of the needle, and you're basically automating a syringe. So thats sort of how that technology in a very iterative way came to be. It was trying to take that injection out of the healthcare providers hands and place it into the patient's hands. That way at a time when you're in that life threatening scenario, you try and remove as much guessing as possible. Well, what we found out was, even though these technologies are somewhat solving that problem, they're not completely solving that problem.

So, as you mentioned, it's difficult for kids to use the current system, so is that the big pain point that you've been addressing - is making this so 10 year olds can do a self administered auto injection?

Yeah, so our thought process is basically three pillars. So we think about affordability, portability, and usability. So if I take you through all three of those, it really describes what the current issues are, and why we saw a space in that market for what we developed. So on the affordability side there has been a lot of talk especially in this epinephrine space about the increase in price - especially over time in the United States - where the EpiPen got to a $610 price tag for a two pack. So you have these devices which are essentially: springs, plastic, and a 15 cent syringe with the drug in there.

It's like the cost of a TV...in your pocket!

Exactly, it's still a price that most people aren't paying with insurance and things like that, but, you know, your out of pocket prices are still just extraordinarily high. One of the things that's interesting there from the affordability side is, even if your insurance does cover one of these epinephrine auto injectors, oftentimes families want more than what they're capable of purchasing on their health plan. And so, you have individuals that want to have one at their neighbor's house, want to have one at school, want to have one in their car. And so you're left with buying them on your own at a cash price - and there are ways to get coupons and discounts and things like that - but it's very difficult for these families to have to focus on that. And then it becomes a yearly purchase, right? It's my kids going back to school, I need to buy another one of these and throw out all of the ones that we didn't use last year.

Why do you have to throw them out?

Yeah, so that's something that is another wrinkle to...sort of big issues that current patients have with devices, and that's on the actual shelf life of the device. So epinephrine is a pretty finicky drug, it's susceptible to degradation in a number of ways. One of those is temperature excursion. So if it's not at room temperature, if it gets too hot, or it gets too cold, the efficacy of the drug can actually go down. If it's exposed to oxygen over time - you've got that plunger and the glass and the needle - and if any of those seal off points around the drug during your year of storage, have leakage of oxygen, then the efficacy of the drug will will degrade over time. And so if you look at an EpiPen today, there's actually a window on there where you can look in and you're actually supposed to be able to inspect the drug prior to performing an injection, and what you're looking for-

While you're like, suffocating and stuff you're supposed to like...make sure it's still good?

Exactly. The hope is that you have patients who will routinely look at their device, take it out and say, okay, it's still good, let me look at the expiration date, let me look at the drug. But we all know that's by and large probably not happening. And then do you expect a patient to be looking at the the drug for clarity and color, right before they're performing injection to save their own life or somebody else's life in a five minute window? Probably not, right? So what happens is, it just becomes a cycle and you say, it's gonna last me...let's say, this year. I'll throw them out, I'll get a new one, and then you start facing that affordability piece as well. I broke it up into those three pillars, because we tried to think about the patient experience. That's really what Pirouette is all about. What issues does the patient have, and how can we resolve those? It goes all the way from procurement on this affordability side to the portability piece - how can we make it so that it's easy for them to bring it wherever they go - to the usability side, when it when it comes right down to the final "This is it, I need to perform an injection", how do we make that easier as well. So we've talked about the affordability side, a little bit about the shelf life and the actual stability of the drug and how that that actually plays into more of the affordability piece as well, and you know, if that can be extended, and that's helpful. When we go to the portability piece, that's actually where we first focused. It was why we started Pirouette.It was a thought process on the existing devices today...are fairly bulky. Most individuals that are prescribed these devices are told hey carry two, especially for reliability purposes when you're talking about a device that may malfunction. Or if the efficacy of that drug has reduced, it may not actually save your life. So carry two - so if you inject that first one and it doesn't work, go ahead and inject a second, right? You think about one of these devices, which is about six inches tall, it's a long one inch wide, pen shaped device, and then there's kind of this 's clip' that will pair two of those devices together. You're supposed to stick that somewhere and be able to take that with you wherever you go.

One thing is that, as you describe this, you make it sound like it's obvious that this is something that could be changed, but I'm sure that when we backtrace to the past 'you', you mentioned that there's a patient-centered design process - like human factors engineering - and that's something I think would be really interesting to understand is the process of how did you start - you and your colleagues - to figure out that this is a problem that needs solving? One thing is seeing the problem, and one is the discovery of that, and then how to figure out a decent solution, or in this case a really clever way of addressing those human centered challenges.

Oh, you bet. So we did it in two ways. So essentially, we started with what do we think the problem is based on our understanding of the current landscape, the current devices just sort of looking there. And like I said, we started with portability. We're like, these things are huge and bulky, how could anyone carry them around? And so we basically thought, alright, how can we make an injector smaller? But your question is a little bit bigger than that. And it's, it's very interesting as well, because you start to think about well - you know, I was telling you guys how these were around in the 70's right, so now it's 2017 which is sort of the time I'm referencing, we started to talk about this portability issue - obviously there's an issue with making these devices smaller, how come nobody's done it? There's quite a bit that goes into that. Some of it is really this whole sort of iteration type design, where you've got something that's working, and it's like, how do we make it a little bit better? These guys have an auto injector, let's make an auto injector. And then if you start to compare all these auto injectors to each other they look the same, they feel the same, they sort of work the same, they have the same general shape. And a lot of that came from...well, it's working, you know, to some extent. With the EpiPen - for example, by 2016, they had captured over 97% of the market - was something that was essentially not the perfect solution, but a solution. So why change that?

Iteration wouldn't be a way to get on the path toward having like a really innovative solution, or do you think that iteration is absolutely sort of a prerequisite activity that could lead to a really game changing medical device translational engineering?

No, I think it was really an economical decision of how much R&D do we want to put into this when we're already capturing huge percentage of the markets, and it's already shown to work. And I think you're right, iterations are great, but at the end of the day, if you want to have a giant leap in this sort of change in technology - or as we describe it, this Pirouette in technology - you kind of have to start with a blank slate, which is what we did, and to go back to that human centric design that you were referring to, we love that. That's what we focused on from the very beginning. And I mentioned earlier, we did that in two ways. So the two ways we did that were - the first was by performing patient surveys. So we literally tried to contact as many patients as possible, who rely on these devices, who have used all the various types of existing epinephrine auto injectors, and we basically performed 1000 of these where we developed a survey, we went out, we tried to get them completed, and we said, you know, what device do you use? What do you like about it? What don't you like about it? Obviously, it was a lot more questions than that. But that was essentially the the basis of what we were looking for, right? What are your issues with existing devices? And then can we take that information and build that into our design requirements? And then start with a clean slate and say, how do we solve this problem? Not how do we make a little bit better device than this one that exists already. So we did that, and then we also brought a advisor on board who's a Board Certified allergist, who prescribes these epinephrine auto injectors on a on a daily basis. He often spends a lot of time training patients on how to use the device. He works with children, trains them on how to use it trains their parents on how to use it. So he sees a lot of the pitfalls with existing devices - what did they do wrong with it. So we worked with him to conduct a small study where he was basically handing a trainer device of the existing technology to these patients saying, okay, go ahead and perform the injection. And then monitoring if this was a real device, would they would have done it right, or they would have done it wrong, or if they did it wrong, here's what would have went wrong. And so we found a lot of information that we really hadn't thought about I mentioned we were sort of really focused on this portability piece making the device smaller, but we built out so much more than that when we really talked to these patients and found out everything that they were really thinking about. I kind of alluded it alluded to this earlier, but really what we discovered was along that entire pipeline from procurement, to maintenance -and by maintenance I mean, bringing the device where you maintaining it wherever you go - and then actual administration of that of that injection, along that entire process, there was essentially this overarching, what we describe as fear and anxiety. So patients were worried about how they're going to pay for it, how they're going to procure it, they were worried about how do I bring this with me wherever I go, what happens if I come in contact with it with an allergen like a bee sting, and I don't have it, what are the options for me there, and then I'm super scared to use this device. That was where it really started to dawn on us that like, okay, you may have removed the health care provider, but you really haven't made this mainstream, so easy to use, that you've removed that anxiety and fear, and there still is quite a hurdle that these patients have to overcome, to go through the process of performing an injection. And even if they overcome that hurdle, we see problems that arise even at that stage. And so from that usability piece, we really focused on two injury mechanisms that can occur during that process. So one of them is an accidental injection, where the device is used upside down, and they can actually get a needle into their thumb, for example. We also call that the lost dose hazard, because you're not necessarily going to be causing much health risks - you do have a lot of vasoconstriction, because of the epinephrine drug that will happen in that location, and you do have to oftentimes treat that thumb or other finger or other digit that gets that injection - but at the end of the day, what the what the scary piece is there is if you're, let's say a dad, and you're injecting your child who just got stung by a bee and you swing this thing, and you've got your injection into your thumb - and we call that the last dose hazard, because now that child doesn't receive a dose, and they still are in a life threatening scenario. So that's very scary. And now you basically have two patients instead of one. The other injury mechanism we looked at was lacerations, which is where you basically have these tall skinny injection devices, and you try and perform an injection, it's very hard to control the position of that injection. So if I show you my pencil here, right, this is typically how you're holding a pen injector, right? And so you're basically making this motion, it's contacting the injection surface, and the needle is then going down into the tissue. But you can see where my hand is several inches away from the injection site, and you have very poor control over the actual needle. What happens is, oftentimes, that injection system can slide and you're dragging a needle through tissue causing a laceration. And what we often see is a V shaped laceration, where the first cut happens, and you try and correct for it, and you actually cut in the other direction. So it's very intimidating, very anxiety driving, very fear driving, and all of these things add up to where when we were looking at our study of patients that were just using trainer devices, in a calm, clinical setting 15% of these individuals refused to actually try and perform an injection out of fear and anxiety alone. And this is something we never thought we'd find.

With a trainer device?

With a trainer device, so there's no needle, no drug, and 15% of people said, heck, no, I'm not doing it. It's too scary. We actually had reports from that study where there were children running out of the room, because they didn't want to receive an injection. And if you're performing an injection on yourself, it's often a little bit easier to maintain control over the injection device, because you kind of know where your leg is going and what it's doing. But if you're trying to perform an injection on a child who's so scared that they're ready to run out of the room - imagine trying to swing this thing onto their leg and hold it steady with your hand several inches away from that injection site while the child is pulling their leg away. It's almost impossible. And so you see research articles now that actually talk about, if you're going to perform an injection on a child with one of these devices, you're basically putting them into a WWE wrestling move in order to lock all motion, and then try and perform that injection. It's just, you know, as we sort of see it, not an ideal solution. And so that's really...

This is a great characterization of the problem and what I think a lot of people even today experience. Do you have a show and tell of what you have, because it is fascinating and it does not look like a needle or anything like that, it's completely different. It's like a hockey puck.

Exactly. So I have one here. And as I show it...

Can you demonstrate on yourself?

I can't demonstrate it today. The version I have is basically a show device for giving pitches and talks and things like that. And unfortunately, right now, with us working remote, the devices that we have that are currently functioning are actually at my CTOs office, and I wasn't able to get one in time for this demonstration. We have reduced these to practice. We have the devices, delivering the drug with the needle extending but unfortunately, those fully functioning versions of the device are currently at at his office. But I do have the device that will show you that process, and I'll walk you through how that how that would work. So to give you that high level view again, we thought about affordability, portability, usability. And as we talk to the patients and perform these studies, the things that we thought about were the patient anxiety and what drives that anxiety. All of those pain points that built up towards that overall patient anxiety, and how can we change that total patient experience? So you're exactly right, our device doesn't look anything like the existing technologies, it's, as we describe it, sort of a low profile disc. You mentioned a hockey puck, we used to call it a hockey puck all the time, but what happens is, people think of the size of a hockey puck, and it starts to grow in their mind about how big it is. If you see it in my hand, it's it's not as big as a hockey puck, it's a little bit smaller. But we tried to find a happy medium as well, because you're gonna have people who need to manipulate this device at the end of the day. You obviously want it to be as portable as possible, throw it in your pocket, take it wherever you go, but at the end of the day, you know, somebody needs to operate the device, use it to administer an injection, and to do that it has to be at least, you know, a certain size to manipulate the surfaces. So the way it works, right...

It's like a can of tobacco, you know, just put it in your back pocket. Probably not a way to sell it to the kids.

Yeah, in terms of size and shape, it's very similar. But yeah in that regard, I think, talks to the points of portability. In terms of usability, we tried to reduce the process to what we saw as low barrier steps, as well as highly controllable steps so that at no point were we driving anxiety for the patient. And our whole thought process is if somebody walks by who's never seen our device before, they can pick it up, read the visual instructions on the top - so we have the graphics that represent those three steps - and say, Oh, that's easy, I can do that, and I can save this person's life with their device in their pocket. So that was really the push on the usability side. So what you actually do is...and the compare and contrast piece...we basically took those tall, skinny devices and went to a short, flatter device. So it kind of will remind you more of a patch pump type injection system, but the big difference is, rather than a subcutaneous injection, we're still fully intramuscular. So even though our device is low profile and much closer to the injection site, we're still hitting that intramuscular injection depth, which brings us back to that direct comparison with the auto injectors of today. So essentially, the three easy steps that we go through are: twist and remove this safety plate - so there's a red safety plate on the bottom. After you twist and remove the red safety plate, you place the injector down on your injection site. In the case of epinephrine, we're talking about the vastus lateralis, so you're sort of top outer thigh, just so you guys can see it. I'll demonstrate it on the deltoid intramuscular location. But essentially you would remove that safety plate, and then you're going to place the injector on to wherever your injection site is. For you guys I'll use my deltoid to demonstrate the injection. So basically you twist or remove the safety plate on the bottom. It's a very easy twist motion, there's a there's a lot of narrowing and ridges on the device and places for your fingers to hold. Once you do that and open the device, it's already correctly oriented in your hand for placement on the injection site. So you would just place it - and we actually use the term apply it -apply it to the injection site. And one of the unique characteristics of our device in comparison to the other injection systems is we have this large, flat surface area that comes into contact with that injection site. And so what we did there is we actually covered that injection site with an adhesive. So we're helping hold that device on location in a number of ways. One is that form factor being low profile and close to the injection site. We talked about having your hands several inches off the injection site before now you can sort of see, you barely can even see the device, right? If I move my fingers, there it is. But if I place my hand on the device to perform an injection, you barely see it, and now my hand is basically flat and pushing up against the injection site, I can actually grab on to my arm and pin that device in between, and at this stage, you simply push down. So it's three easy steps: remove the safety cover, apply that device onto your injection location, and push down. And one of the really unique things...so we kind of, you know, we don't want to get in any copyright trouble, but it's basically like pushing a big easy button. So we really describe it as trying to reduce the administration of performing an injection, the administration of injection, to as easy as pushing a button. And really, that's what the whole process was driving towards by reducing that anxiety, making it so simple. And one of the unique things is when I push down to perform an injection, that force that I'm pushing down with is not actually pushing the needle into the tissue, it's not forcing the drug out of the device, it's simply activating the device. So no matter how fast you push down, how slow you push down how hard you push, all you have to do is bottom out that device, then when you when you push that button down, the device is going to perform the injection for you with a tuned amount of force every time the needle is going to extend to the same length to get to that at that same intramuscular depth, the same amount of drug is going to be delivered. So all the guesswork is gone, all you've got to do is push down and it does everything else. After you let go of that device, it actually pops back up to its height before you push the big button, and it locks out completely, and three flags appear circumferentially around the device, with a big red flag with white letters saying used. One of the things we wanted to avoid is the issue that we learned about when talking to patients where devices that they had previously used and then put on the ground, someone will come by and have no idea that that device has already been used and try and use it again. So this device locks out, you can never push it down again, you never see the needle before, you never see the needle after which also removes anxiety. It's a much less assuming shape, so you know, one of the things we heard from patients as well was "The whole thing looks like a needle to me, it's super scary". So we tried to remove that as well, and it all was able to build together - the device was smaller to begin with, it was lower profile that had benefits for portability, that had benefits for usability. And then at the end of the day, we call it an elegant design, because it uses as many standard off the shelves, technologies in the pharma industry that are already used today, we tried to streamline that entire process, we tried to streamline the manufacturing. So you have this improved functionality, but you don't have big cost drivers behind that. So you're in terms of your cost of goods, you're basically the same as other injection technologies, but you have this leap in functionality. So that's why we call it an elegant design as well.

This is really clever engineering, though, as we've got engineers in the room here. We know that to build something cool in an elegant design, there's a satisfaction in that. But that's also not the only battle that you would have to be able to translate this to be able to work in the market to get it - like if I were a loved one could benefit from this kind of device. Can I get it now? And if not, what's the pathway that you're pursuing to be able to get it to people who need this?

And that's always something that is always tough for us to hear, because we'll talk to people who rely on these devices and the question is, when can I get it? At the end of the day, it's a long road for medical devices, and what we have here is a combination product, so it's an injection technology that we've paired with a specific drug and that has to go through regulatory approval, and when we're talking about here in the United States, that's FDA approval. For our specific device, to dive a little deeper there, we're talking about a streamlined pathway, but it's still, a very rigorous pathway - and well, it should be. And so there is a lot of time and a lot of money that goes into taking a device from reduced to practice to a point where you know it's safe and effective for consumption by the patient. So we're not against going through these steps, it's just that it is a process that takes a lot of time. And that's the hard part, when we're talking to patients, we tell them it's a great device, it's on the way, but, there's a lot we have to do between now and FDA approval and going to market and bringing you this device. And so, to give you a little bit of perspective on what has to happen is so we talked to the patients, we performed our studies, we, took all that information, we put it together, and we were able to convert that into design requirements. And then we go through our preliminary design, our detailed design, we go through a lot of iteration in that design based on putting some of those early concepts, early prototypes in the hands of the patient. So these are all pieces of the this pipeline that we've done. And then based on that information, we went back, change the design to make it even easier, and that's how we got to these three super streamlined, easy to overcome steps. And the form factor that we have today, not making it too small, but making it something that people can actually work with and handle, especially if it's a patient that may have limited dexterity or whatever. So all these things that continue to come up, and then we took every single component and we went to potential manufacturers and we said, hey, you know, what would it cost to manufacture one of these? And how would you do it? What would it cost a manufacturer a thousand, a million, 10 million? And you go through that process of what are the cost drivers? And can we change or remove those major cost drivers while still maintaining the reliability and functionality of our device. And so we did that on a component by component level. And now we're going through that process on a larger scale, which is a manufacturing and assembly scale, where we're actually going through these process developments to understand, okay, we can do this with one device, but can we do it with millions and millions of these as we would continue to scale this out for epinephrine or a future application. And so, by doing that we continue to increase the elegancy of the device, the reducing the cost on a per component basis, but also on an assembly basis. But from here - where we have to go after this stage that we're in right now, which is going through that process development for that large scale, manufacturability - the next step is to go through a full litany of testing that is required by these regulatory agencies in our case, we're talking about the FDA, for example. So, there's certain tests that we have to perform, which are, as we describe them, kind of in different buckets. But some of that is what we would describe as human factors - which you sort of alluded to Jonathan earlier - which is you went and asked the patient what they wanted, or what they didn't want, and then you set that into your design requirements, and you built something, but how do we know it's really addressing what they were targeting. So that piece of testing is literally putting it in the hands of a user and saying, I'm not gonna tell you how to use it, you go and use it, and we're gonna watch you. And basically, it's the classic one way mirror, and you're in a scenario, whether it's a school cafeteria, or whatever, and that users basically left to their own devices to, either have the device sink or float, did it work the way we thought it would work?

They're left to your devices.

Yeah, they're left to our devices – yeah, exactly. So that'll be a big and exciting step. And one of the reasons why we did a lot of that iterative testing early on, because we wanted to know going into that, hey, we want to be pretty confident that this is going to be successful when we get far along in this in this adventure. So that's a big chunk of the testing that has to be performed and all that data has to be collected, and presented to the regulatory agency for approval. And that's one piece of it. Then another piece is actual device performance testing. Does the device perform exactly the way you said it's going to perform? And does it perform that way over and over and over again. When we're talking about an emergency device that's going to be used to save a life in those five minutes, there's a very high bar for reliability. You heard me mentioned before that a lot of these devices, they say, hey, carry two of them. If it doesn't work, the first time or the efficacy has dropped, inject a second, we're talking about trying to have such high reliability that you could potentially just carry one.

What kind of number would that be like, one in 100,000 failure rate, or what?

Yeah. So it would be a lot better than that. So we're talking about what we describe as five nines of reliability. So that's 99.999%, so to actually hit that, you're talking about, specific statistical methods in order to look at that sampling for your testing. And you're talking about very extreme reliability. One of the things that you can already - if you start to think about that process of developing and manufacturing these devices - you could really already basically just remove humans from that process. Because if you put somebody in there who's assembling one of these by hand, you're gonna have a hard time hitting high reliability levels. And so this is a computer automated process that's putting devices together.

So a robot has to assemble the entire device?

Yeah, not only that, but you're going to be checking subsystems throughout that entire assembly process. So your devices put together via complete automation, and at the same time, each of those steps are verified, whatever that method is, you have to make sure that, okay, this one that we just put together was put together correctly. So you basically have those in process checks throughout that piece, as well, which is...it kind of gets back to something that's on the top of all of this...which is as a funding piece. So, it takes a lot of time to perform this testing, it takes a lot of time to go through putting that data, into a format that needs to that's easy to be reviewed, easy to be understood, easy to be seen. You take a lot of time in the manufacturing process, you take a lot of time in the design process, all of it's a lot of time, but it's also a lot of money, and a lot of upfront capital. Fully automated assembly lines aren't cheap, in general, when you're talking about a combination product, the ballpark I like to throw around is $70 million and 10 years to develop one of these types of devices. So it's a very uphill battle. Us being a smaller, more nimble company, we try to undershoot both of those, so, do it faster and do it cheaper. And a lot of that relies on us as founders and employees to figure out ways in which we can do things ourselves rather than outsource. And one of the reasons why I love having a founding team that's made up of engineers with great engineering backgrounds, we didn't have to outsource that early design process, we knew and understood human centric design, we knew and understood that combination of humans and system. Where does our device lie in that process? And how do we actually design each of these parts? How do we design the total system? How does it get put together? If you outsource that you're talking about a lot of time and a lot of capital that's required, in addition, and if you can do it on your own, you save a lot of that you can stay much smaller earlier on, which we tried to do and remain capital efficient through that process.

The relationship with Covestro, is that to help on manufacturing, and the tactical aspects of the design to the point of like figuring out which kind of plastic is useful that maybe your founding team of engineers may not have known that certain types of polymer chemistry would work for this medical grade application. Why partner with a large company like this, or was that the only pathway available?

That's a great question. One of the sets of testing that we didn't talk about beyond that device performance testing is looking at the materials that are actually in your device and making sure that those aren't going to irritate somebody's skin or effectively cause a reaction where we're trying to save a reaction. So one of the things that we can do by working with one of these resin suppliers is basically say, okay, we need it to be medical grade from the beginning. And already that de-risks a huge portion of that downstream testing, because that plastic material has already been shown to effectively pass that testing. And then by combining multiple types of that plastic material, we know that we're not introducing any materials into the device that are going to harm a potential patient. So we start there, but then exactly what you mentioned, which was can we also rely on their expertise to say, okay, hey, we need a part that looks like this, here's how we designed it. And here's the forces it needs to stand up to, needs to be medical grade, what do you got? So they can come back and say, hey, we've got these two resins, that can withstand the huge forces that you're talking about, and then fit all the rest of your requirements. And that's...I love the video you're alluding to, because I'm not sure where I came up with that on the fly, but I said essentially, what we're trying to do is pack a big punch into a little package. And that kind of goes back to what I had mentioned before, with the existing devices being these big, tall, skinny devices that have these huge springs, and they're basically pushing a ton of force through to get to the intramuscular space. It's not easy to have to have an automated system to deliver a needle that deep into the tissue, and then get your drug to bolus through. We cut off this device an inch above the surface, and we still need to get down to that depth. And so some of our parts that are smaller, because we're in a little package, need to withstand fairly large forces in order to do what we're asking them to do reliably and not fail. So that was sort of that relationship there, it's like, you know, we need some really good resins, what do you have, and that was that,

I think that's something really important and for fans of the podcast, the YouTube channel, if you're looking at medical device design, and you mentioned earlier that, you know, we, we pretty much had to start with a blank clean sheet design for this kind of problem.

Yeah.

But the the asterisk on that, I'd say is that it's a clean sheet but with some very specific design criteria that you're thinking of designing for manufacturability. So we do have a down selection, it reduces your search space, which is really helpful to to be able to come up with a new type of medical device. And so I'm curious then, given that you're hitting targets on reliability, durability, shelf life, and affordability, have you considered not just working with the FDA, of course, for, say, the United States market, but also in some of the perhaps lesser developed or less mature medical ecosystems around the world...because I know I've talked with medical device companies that are like, oh, we're gonna test it in somewhere else, and get a lot more sort of clinical numbers earlier there, and then come back to the FDA.

In terms of our strategic vision there, it's a little bit different from a more typical med device space where that is an option. And the reason I say that is the first place we looked at, for a number of reasons - not only because it was the first introduction into auto injectors - but the first place we looked is epinephrine. So there are a number of reasons why we're talking about the United States first. So one of them is the actual regulatory process to get an approval for an epinephrine combination product is a little bit more streamlined than just a typical combination product. And that's because the FDA understands and knows about some of these existing issues, and wants to see more competition, it helps with innovation around the device, the functionality around the device, it also helps with affordability, with additional players in the space. So I think there is some pressure to see - especially based on sort of the you know, media coverage and political pressure - there's definitely pressure to see new devices in this space, and I think that's why we have started to see new devices in this space as well as you know, potential new incumbents like us are coming into the space. And then the other piece of that is the market. So the United States today is in the vast majority in the epinephrine auto injector market. And so we're pairing the pathway to approval with post approval, revenue generation capability and making our decision for FDA US market first.

Is that because people in the United States have more allergies, or is it these products sell for more? Why is the US the biggest market?

There are definitely different factors. Some of it is awareness, the actual prescriptions, the prescriptions are growing at about 8% annually. And that really is based on an awareness of these allergies. Even if you're not an individual who's that "five minute, a fatal individual" and you still have some allergic reaction to it, oftentimes, you'll still be prescribed an injector, because at the end of the day, we don't know how these allergies are gonna be progressed. If you're stung by a bee one day, and you're fine, or you're having an allergy, but you're, you're okay, and you can work through it with some Benadryl, for example, that doesn't mean that a month later, it's going to be that same process. And so there's that thought process there. And then one of the other big allergens that we talked about is allergens to medication, and we we have an elderly population as well that takes a lot of new medication and a lot of medication in general, and those individuals are also often susceptible to severe allergic reactions with their medication.

As we come to the top of our time together, Conor, you've been through a lot in this process. Is there some advice that you'd have for the past you, the up and coming engineer who's just like, "I think I might try to build a medical device and save lives". What advice would you have to that person?

Yeah, that's a really good question. So I think in general, some of the things that I did that were most helpful for me which is advice that I would give is, first of all, be patient, these things take a lot of time and just getting the design done and getting reduced to practice, that's only the beginning, and we've talked a lot about that. So I think be patient is one. Another is surround yourself with people that can help make the barriers to the finish line lower. So if you can pair yourself up with somebody who's gone through this process before or has been through the FDA process before, whether it's with a combination product or not, or has experience working with a lot of these larger pharmaceuticals, all of that type of experience is really useful. And I think one of the things that we struggled with early on was, hey, we've got a great new device, but we're going up against what is a thriving industry where there are a lot of large players who are trying to hold on to or grow market share, and we need to be able to play in that space, and we need a lot of power in our corner to do that. So I think that was something that I would always say to somebody who's getting into this space is do your best to reach out to people who you think will be really interested in what you're doing, want to help you and can be effective in reducing the bar that it takes to get to to the finish line.

One question or comment is that I understand- this is a topic shift. Conor, I understand that you have a publication coming out the Encyclopedia of Bioastronautics, is that right?

Yeah, it is.

What is that?

What is that?

I'll go back a little bit more and just give you guys a little bit more of a story of my background. I think that'll address what that is and why it's important to me. So I grew up in Southern New Hampshire, right next to a grass strip airfield. My window was looking at the airplanes go by all day. So I really was into into aviation. I wanted to be a pilot. I started by flying a little RC planes and eventually went on to get my pilot's license and my undergrad degree was in aeronautical engineering. So basically the basis of mechanical engineering, but you're really applying that to the development of flight hardware and, and planes in general. So that was a lot of fun, and interestingly enough, when I was in undergrad - this was at Clarkson University in upstate New York - I also added a minor in biomedical engineering, I was really interested in the medicine side as well, I worked on a vibrotactile feedback system for lower limb prosthetics, I was always really interested in that combination of taking the human body and medicine and combining that with engineering and during that period, I started to think, hey, you know, maybe I want to go to medical school and become a physician. But after getting involved in a lot of these projects, in undergrad, these engineering projects, I was like, this engineering is way too fun, I want to stick with this. So I ended up going after a PhD, and I basically settled on what I found to be the perfect PhD Program, which was called the Health Sciences and Technology program. It's a joint MIT and Harvard Medical School program, where essentially you're doing just that, you're combining engineering with medicine. It actually came out of a conversation with MIT boosters who wanted MIT to start a medical school and MIT basically went through some analysis and said, hey, we've got Harvard Medical School right down the street, rather than starting our own, let's just collaborate. And the thought process behind HST was, rather than taking physicians and trying to teach them to think like an engineer so that they can solve problems in the clinical setting, they took engineers, and showed them the clinical setting and brought them into that world and allowed them to continue to think like an engineer and solve problems, but understand the clinical settings so that what they're developing didn't go to the clinical setting and then just become obsolete because they didn't really understand that process. So it was really the marriage of the two which really fell into what I was doing. But as part of that program, you're able to choose a concentration - my concentration was, of course, aeronautics and astronautics. So I was in the AeroAstro program at MIT, and then within the HST program, Health Science and Technology, there are two specialized training programs. One is in bio-imaging, the other was what they call this bio-astronautics training program, which is going deeper from Aero Astro, it's the it's basically the human body in space. So my expertise after my PhD, and the work that I had done there was really on anything that can happen and does happen to the human body in space. So I really was able to pull all that love for aviation, aerospace, as well as medicine together at the right time. And actually one of my clinical rotations was with the flight surgeons at NASA. I was able to do a lot of really fun things during that period that it was just a blast, got to work with the spacesuits, that was what my thesis was on - sort of developing a spacesuit - which was really that close marriage of the human body, medicine and the technology and engineering side. So it's been a lot of fun. But yeah, one of the things that I worked on while I was part of that program was the Encyclopedia of bio-astronautics, which was basically an opportunity for me to work with one of the professors at MIT, Larry Young, as well as with the National Space Biomedical Research Institute and Springer who is publishing this work, as well as all the SMEs, the subject matter experts in these space spaces and talk to them on a daily weekly basis, take their knowledge integrated into this work, and that was probably one of the best experiences I had. Having the ability to interface with all of these amazing people who were the experts at the top of their field in bio astronautics, which I had just got my degree and help put this work together. So, yeah, it's very exciting.

That's so cool. Let's hope that maybe eventually close the loop and be able to send some of Pirouette Medicals medical devices up into space, because even though there might not be as many bumblebees up there, I mean, it's adverse conditions.

So it'll work in space, right?

It will. And, we're talking about epinephrine first, but there are there are obviously other applications that would be very well suited to an easy to use and portable injection system and I think mentioning, for example, space, there is a great way to just sort of wrap that all up into one and say there's plenty of other places that a technology like this can go as we think about, you know, how do we expand beyond epinephrine? How do we expand beyond the United States? And maybe how do we expand beyond the world?

Well, that wraps it up for episode. Thank you very much for joining us today, Conor.

Thank you, Conor.

I'm Conor Cullinane, and I'm one of the co-founders and CEO of Pirouette Medical. Stay tough!