Meet Josh Makower. The Inventors of Aesthetics Series No. 2

Dr. Grant Stevens

Hello and welcome back to the technology of Beauty, where I have the opportunity to interview the movers and shakers of the beauty business. And today is no exception. Today is a very special day. Today we get to interview Josh Makower, who flew down from San Francisco just to be with us on this show. Hi, Josh.

Thank you so much for joining us. [Thanks for inviting me.] I've been bugging you to do this interview for over a year. You have, and I'm happy to be here. You're gracing us with your presence. I cannot tell you how happy I am.

Josh Makower

Yeah, no, I'm happy too. I'm, we were waiting for some important, exciting news and we were ready to share. So I'm ready to be here.

Dr. Grant Stevens

That's right. Now you have a very interesting background and there's a lot of listeners and viewers right now who don't have a clue if nothing else, that you're a doctor. You went to med school. Yes, I did. And there's a lot more to it. So let me start with this. Where did you grow up? Where'd you go to high school? Let's start with that.

Josh Makower

I went to Ramipo Senior High School and in in Rockingham County, New York.

Dr. Grant Stevens

So you grew up in New York? Where'd you go to college?

Josh Makower

I went to, I started my college at Case Western Reserve University, and then transferred to m mit, finished my degree, my bachelor's degree in mechanical engineering there.

Dr. Grant Stevens

Okay. MIT, so you got a mechanical engineering degree? And then you decided to go to med school?

Josh Makower

I did. I wanted to use that engineering degree to create things for improving medicine. And so I thought that I should go to medical school and learn about how medicine is taught to doctors. So that's why I went to med school.

Dr. Grant Stevens

So when you went to med school did you know you would not be a clinician?

Josh Makower

Not I went to medical school thinking I would be a physician that. Would be involved in creating things like you. I actually, I.

Dr. Grant Stevens

You'd be me when you grew up?

I was I did,

Josh Makower

wasn't able to be. So I, the next best thing. The next best thing. But no, I wanted to so I did go thinking I'd practice medicine in it also create, new technologies and that kind of thing. And there weren't a lot of role models that did that at that time.

Dr. Grant Stevens

That's why I'm asking about it. And there's a lot of people watching this. The cautious of the world. And young folks that have trained with you and who spent a little time with me, who now have some mentors like you to follow in. But I know you blazed a trail that had never been done, so that's why I want to pull outta you.

Yeah. So off you go to med school four years,

Josh Makower

and you graduated.

I helped, I did graduate. I do have my degree. But I decided at that point I wouldn't match and I would at that point transition my career to use my MD to create new technologies and try to improve health that way.

Dr. Grant Stevens

Okay. So yeah, I didn't pull outta you. Where'd you go to med school?

Josh Makower

Oh, nyu. Yeah. Yeah, in the city.

Dr. Grant Stevens

Okay. So match is when a person decides to do an internship right. For those of your non-physicians. So you decided on your fourth year of med school or something. I've got the medical degree. I've got my engineering degree. And where did you go after med school?

Josh Makower

After medical school. Hunted around a little bit and then landed a job at Pfizer. I, so I was.

Dr. Grant Stevens

A little pharma company.

Josh Makower

At the time they were device company as well. They had a, had, they had about a $2 billion device business back then.

So how Medica orthopedics. Schneider, interventional cardiology et cetera, et cetera. They had several divisions and devices and I thought, no better place to go to Pfizer, which had both drugs and for and devices as a place to innovate and create. And so I was really excited to to go there.

It wasn't until I walked in the door that I learned that the device division never talks to the pharma division. They're like, I wanna do this. Yeah, that's not gonna happen. But anyway, that's why I went there.

Dr. Grant Stevens

And how long did you stay at Pfizer?

Josh Makower

I was there for I think it was a good solid, at least seven years. They did support putting me through business school, so I went to Columbia Business School Executive Program, they helped me do that. And really actually the experience that I had with Pfizer gave me an opportunity that has actually. Transformed my entire career. And that was the guy that hired me was a guy named Hank McKinnell.

And at the time he was the CFO of the business. He's the one that pulled my resume out of a stack, and he was in charge of strategic planning at the time. And then he later became the ceo of Pfizer. But while he was the cfo he brought me in, gave me this job in business development and technology development on the medical device side.

But he lit literally a week into me being there. He calls me back to his office, says, I got a special project for you if you have time. And he asked me to. He said, we buy all these really creative, innovative, and rapidly growing businesses, and yet after we acquire them, they suddenly stop innovating successfully.

And their growth rate slow and their innovation slows. And I want you to figure out why. and if you have time. And I was like, oh yeah, I'm doing this. So it was a great opportunity because I went and I interviewed all the founders of those companies and their management teams. The ones that were the before acquisition group.

And then I interviewed the presidents and the then the teams after acquisition and just ask them a lot of questions about, how do you find your ideas and where do you go? And when I realized it was really interesting, I realized that, when they're in the mode of being a sort of like about to be a startup, they're really trying to solve a problem, , and then they're just bringing whatever technology makes sense to bring to that problem.

But after they're acquired and that's when they've already been successful and they made a balloon catheter to treat, coronary artery disease or something like that, they become a balloon company. And now they go where else can we. use a balloon, which is a very different proposition than trying to solve a problem.

Because when you have a ball, when you have a hammer, everything looks like a nail. Excuse me, basically. And so that difference, I basically said, I think this is the big difference, is that they suddenly get pigeonholed into this technology. And at the time the business school think was economies of scale.

You find other ways to leverage your manufacturing base, your et cetera. And I think that led people down this unfortunate path of where they would basically try to find new products for pretty much what they're already making, rather than saying, you're my costume. What else do you need?

And it doesn't matter if I make that today, how can I make that go do it. And and that as a natural course leads to very incremental innovation. So that's why the big companies, for the most part, do incremental in innovation, but they don't really do breakthrough innovation that much.

And so identifying that difference, I came back to Hank and I said, this is the difference. And he says how can we do breakthrough here? And I said I think the way we would do it is basically you take a team, tell 'em, focus on the problem, let's go and get the problem identified.

And then don't limit them to the existing technologies and solutions that we have. Let them explore which is the best fit. And so we designed a program inside of Pfizer to do that and that framework, which I later, which I did with Pfizer when we created a number of technologies there. And spun them into the divisions.

But then after was the methodology that we used for my incubator, explore Med. Mul. And I still use it today. And then this is also what I teach at Stanford. So that thread, that process that we came up with at Pfizer turned out to be my whole career. Like that moment.

Dr. Grant Stevens

And you, so you stayed there at for seven years. And then did you go to come to the West coast and start?

Josh Makower

I did experiment, yes. First a stent I hooked up with new enterprise associates at that time, back in 1995, they John Nira and was the general partner. wrote a small check to, to invest in explorer me on this idea that this, crazy young guy with who, who had this process was gonna create, deal flow for them, and and basically I started on the East coast, but ultimately brought it all to the west because that's where I felt like innovation was really happening. The Silicon Valley area. And moved out in 1996 and that's the, the beginning of explore mode and all the companies that we've produced since.

Dr. Grant Stevens

So the way you approach it is you identify a problem. And you put the best minds and horsepower to solve the problem.

And know, and I know you solved a lot of problems. So let's go back to the beginning. And you've had a chance to see this first hand. That's gonna come out later. But was the first problem. Hearts and vessels. And it was, yeah, it was. My research says that it was.

Josh Makower

Yes, it was actually the very, very first one was a urological problem, which was and that company was bought so quickly, no one ever knew about it.

That technology was called Endo Matrixx. That was actually the very first company that experiment created. And that was for incontinence. And it was an alternative bulking technology too. to bring the urethra more into opposition around the area of the sphincter so that the sphincter contraction could be more effective.

And there were other bulking agents at that time, congen. As a, which is also for aesthetics I'm sure, but yes, was being used. But the problem with that is it's you squirt it in and then as soon as you take the needle out, it squirts right out. And of course it's a bovine collagen, which can, potentially trigger immune responses.

And then also it doesn't last that long. It gets degraded and all this kind of stuff. So this was a, essentially utilizing a suture or thread and fold using it through a needle, but folding it as a bulking a little what's inside of a golf ball, like a multi folded strand. And and that would serve the bulking agent.

And that was bought by CR Bard. So that was our very first one. The second one was our cardiovascular one, which was much more challenging.

Dr. Grant Stevens

And what did you do? What was the problem? Stenosis of coronary vessels. That was basically you said, how do we keep 'em open or was this the first stent?

Josh Makower

No. So at the time when we came up with this the first stent had been introduced, which was the Palmaz-Schatz stent. It was a very rigid stent, and it could only really be applied to very proximal vessels and really only straight vessels. And as you probably know, vessels are very torturous.

So the, it seemed that the stent saying, this sounds ridiculous now knowing how technology evolved, but at the time, that being the only stent that it was, seemed like it was gonna be limited. And so still coronary bypass and all of those Traditional techniques were still all the rage.

And people were talking about how do we do coronary bypass minimally invasively? So companies like heart port and cardiovascular systems or cardiothoracic systems were little companies that were trying to do coronary bypass, but we're using ports like laparoscopic surgery, percutaneously.

Yep. And I looked at that and said, I wonder if there's a way to bypass coronary vessels completely percutaneously using catheter techniques where we could bypass the vessel. But, everyone's down here at the groin with little catheters that were threading back and forth rather than cracking the chest rather than stopping the heart rather than all those things.

That was the speck was wouldn't it be great if we could bypass. vessels totally percutaneously. And that was the vision for trans vascular. And and so we developed really from scratch, an array of tools. Like we, we had to make connectors to connect vessels. We had to make devices that would navigate in and out of blood vessels.

We had to design from scratch devices that were meant to reroute flow. Because the basic idea was that if you look at the surface of the heart, if you were to put a, like a model of the heart on our, on the table right now. And you'd look at the surface, what you'd see is this beautiful main left main coronary artery sitting there right across the anterior surface of the heart, and then right next to it, this nice big blue vein just there right next to it. And so the idea was, can we, for like the, for areas where you couldn't get to with a stent, can we come upstream, pop over to the vein, connect those, go down, come back, connect the distal vein and basically just use that venous segment on the surface of the heart to, it's a bypass.

Be the bypass. Like the bypass materials right there. That was the idea. And and so we had to develop all the apparatus and we, we did it in animals. And it was a little challenging, it was a little challenging, but ultimately what happened was with that company is that the stents evolved much quicker than I anticipated.

So by the time we were really ready to do humans. You looked over and you said why would you do this complicated thing if you could just get this nice little thin flexible stent down there? Yeah, that wasn't the way it was when we started the company. It was this big rigid Palmaz-Schatz stent.

But by the time we had gone through all the animal studies and all the development, the basic idea of bypassing proximal lesions, but actually bypassing them no longer made sense. So then we were stuck with this idea of what do we do now? And we redirected the company towards using the core tools for saving limbs, essentially. And that is where the technology's used today.

Dr. Grant Stevens

So the, for the jump grafts or the where the venous interposition graft? But let's go back before you tell me where it's at. So there you are, and you're doing basically a version of a cabbage or a saphenous or a, or even an ima, You're basically doing a vein graft, jumping over the clo clot graft.

But in order to get to the point where you were doing the stent, you had to get rid of the clot.

Josh Makower

No. We left the the lesion in, just like you do in the bypass. You don't try to clear out that lesion. We would actually bypass around it.

Dr. Grant Stevens

With the stent even?

Josh Makower

No. The, no. With your vein, you did our stent went connected artery to vein, and then the other stented vein back to artery. So it was a, it was, like you said, it was a jump graft. Leaving the big lesion in between untouched.

Dr. Grant Stevens

Okay. And then did that change at some point, didn't you develop a stent though? They went straight intra arterial and didn't touch the vein?

Josh Makower

We, we the stents that we developed could be used for regular stenting. But they were specifically designed to be able to traverse this artery vein gap. But where the technology went ultimately was to allow for, where it's used today, the, today it's that technology's owned by Phillips, which had acquired volcano, and Volcano acquired the Medtronic technology, and Medtronic had bought trans vascular.

So it's but it's still available today. And where people use it is when they're trying to wire a lesion in the leg. And it's a very diffuse, calci difficult lesion in, let's say the superior saphenous I'm sorry, the femoral, the femoral the femoral vein, and they get the wire down through this vessel, but then they're on the other side and it's not in the vessel.

It's wound up being jammed into the sub intima in that wall. They use our technology to get in there, look around, see where the actual lumen is, and then pop into that lumen. So it allows for traversing back into the vessel, and then they put a stent in and they squash the lesion aside and then you basically can, save a limb that way. That's how it's a, it used for that purpose these

Dr. Grant Stevens

days.

So peripheral vascular stent. Yeah, peripheral vascular. I pretty much. Now I know there's been a bunch of other problems you solve, so let's keep moving. When did you get to the pro- was it a prostate or what was the next one?

Josh Makower

The next one, which was probably the beginning of sort of me figuring it out, those two first companies were very challenging and and I learned a lot. I actually have learned a lot in every single company, honestly. But the next one was ENT project. Treating chronic sinusitis.

This is a company called Acclarent, and there we again, need finding saw that, the drugs don't really work that well for chronic sinusitis. And when you finally wind up in the surgeon's office, the minimally invasive quote unquote procedure that they do is FESS, where, functional endoscopic sinus surgery, where they take these large, rigid, straight tools and go into your nose and essentially rip out and cut bone and tissue to open to try and find their way to the sinuses, which are down these torturous pathways.

And just to open up the opening that drains to allow it to drain. And it's very bloody, very painful. It actually can cause a lot of scarring, which produces a disease worse than the original because you get scarring now it's closed, like a door is shut.

And so we saw all that. We said there's gotta be a better way. And the insight there was to understand these torturous pathways and say, maybe we can approach this just like we do in the cardiovascular system with some little catheter that could navigate to the place that needs to be opened.

And then just open that maybe with a little balloon, just the part that needs to be opened so it can drain and not have to cut all of this bones and tissue. And that was balloon sinuplasty. That was a claret. And that was a great success. That was the first time that everything all came together.

We certainly had our struggles along the way, but it, but clinically it worked. It was great for patients. It was minimally invasive. Minimally invasive. It was actually less expensive for the healthcare system cuz you could do it in the office. And you could really treat, and I've actually had the procedure myself so it actually helped me too. It was inspired by my own problems with chronic sinusitis.

Dr. Grant Stevens

Interesting. Interesting. Okay. And thereafter then the prostate one.

Josh Makower

Then the prostate one. So the situation there was. Lots of drugs for benign prostatic hypertrophy, which is the condition that affects the majority. It's the most common condition for men over the age of 50.

It's a enlargement, a benign enlargement of the prostate gland that makes it more difficult to urinate. So basically, you are going to the bathroom a lot. You can't finish a golf game. You wake up in the middle of the night, it disrupts your sleep, it disrupts your life. It's a quality of life disease, but ultimately it actually becomes worse than that.

If it gets very severe. It can result in bladder weakness and injury so that your bladder becomes damaged and then you have a real problem and you can't actually urinate without a catheter. And that's a big problem. So you do want to address it. It isn't just a quality of life problem because if it's allowed to persist to get this much bigger physiologic problem and even, infections and stuff.

So the way it was treated historically was drugs which are. not that great. They don't really, they aren't that effective. They have lots of side effects, like lightheadedness and, all sorts of things like that. And then the other alternative is to get what's called a turp, a trans urethral resection where they go in with a tool and it's carve out your prostate from the inside, which is very bloody and very painful, and also can produce impotence and incontinence, which also isn't good.

So that's the situation. And then a lot of people had tried to do minimally invasive things. They tried microwaves, they tried all these things, and those really never took on. And everyone believed that there was really no minimally invasive solution for prostate. I'd say, but the time that we were going at this people were like, why are you even wasting your time?

Everybody's tried. They've tried microwave, they've tried all the ultrasound. Everybody's tried everything. And why go after this? It's, everyone's failed. And, but. This gets to why this methodology of approaching problems is different. Because we don't just look at the physiological objective, we look at the whole patient.

We look at the doctor.. And as you and I have worked on project that we, when we're approaching this, we aren't just thinking how do you fix that clinical issue? We're thinking about what does the patient really want to experience. What does the experience of the doctor, and when you look at it that way, you realize, hey, microwaves actually do work, but when they put the microwave in there, blast the prostate with all this energy and create all this inflamm.

It makes the patient worse for three weeks, which means that they're calling their doctor saying, this is not good. I've gotta wear this catheter for three. Are you kidding me? And then the doctor's not happy. And then, and by the way, the doctor didn't have to even engage in the procedure, they put the catheter in, push the button, they say, I'll be back in the hallway.

You just have to be cooked for a while. It was just like they weren't engaged. So you look at that whole scenario, now, follow these patients out. Six months looks great. Their prostate's smaller, their flow is better. But are they telling their friends, you should go get this? Absolutely not.

No. And are the doctors saying, Hey, we should do this thing. No way. So that's why taking all the stakeholders into account and creating what we call a need specification upfront and being really thoughtful about, there has to be certain parameters for the payers, certain parameters for the doctors, certain parameters for the patient, but not just the.

What's the flow rate? It's about what's the experience. And so if I were to say what we tried to do is we said, how can we do a procedure where people can jump off the table and pee? And they don't have to take any drugs and they're not gonna get a catheter. And they're gonna be good for years.

Many years. Maybe it would need to be repeated five years later. But can we get 'em like five years of not having to deal with their prostate and back to the quality of life, sleeping through the night, playing a whole golf game without gonna the bathroom. Can we do that? And then for the doctor, can we give them something where they're engaged and they're involved and they have an opportunity to sculpt the procedure for that patient and feel like there's a reason why I went to medical school.

I can do something.

Dr. Grant Stevens

I'm solving a problem.

Josh Makower

Yes, I can solve this problem in a unique way for that patient. Not just push a button and walk out of the room. And then can we do it in a cost effective way so that we actually save money, bring people out of the or, and give them better. So overall, all those stakeholders.

And that's what NeoTract is. It's a way basically to. The device basically allows a doctor in an office setting with very local anesthesia to go in push the prostate aside, open up the urethra, and then tack it in place. And then you do the other side and you tack that in place. And if it's a big prostate, you get maybe a few more tacks than that, the tacks heal over.

And so you get this durable opening within the urethra that's allows for flow and patients are in, can jump off the table and pee and they can go home and they don't have to take any drugs. And for the most part it's for the vast majority of people, I have a really good experience.

Dr. Grant Stevens

So it's another tube that is opened. And kept open. You guys are you starting to see a theme here? There's a theme here. We got the tube. There's a lot of tubes in the body. Tubes, the sinus, now we got the prostate. Trust me, there's more tubes to come, why of tubes tube? Did you keep the same engineers with you as you went company after company?

A few of them. I added the good fortune of getting to know some of 'em, which, there's, you're not a one trick pony. No. You did one and then another. Yeah, another. And we're just starting down this road, guys. But did you tend to keep the same engineers? Only going forward.

Josh Makower

Not all, but some, and I'd say they recycle back in to the businesses. I bet, because I think the reason for that is we try to create a culture that's fair and that people are recognized and rewarded and appreciated and and they get a chance to accomplish something in their careers that matters to them.

Yeah. It's exciting. Solve problem problems. When you do that, it's like, why not join up again? So there are many of my colleagues who are still in some of these businesses, That, when they start to think about what's next, they gimme a call and say what else we got?

Yeah. And I've worked with some a few multiple times, and then some find their careers and they're happy and they stay where they're in those businesses, and that's okay too.

Dr. Grant Stevens

Yeah, that makes sense. Okay, so now we're gonna leave the prostate. Throw another one at me. Yeah, I know of a few. There's something having to do with the vagina now.

Josh Makower

There is. We have one of those we could jump to that one. I could talk about a failure if that would be helpful.

Dr. Grant Stevens

Yeah. At some point. I was gonna get to the failure. There's only been one that I'm aware of and it's not truly a failure. In my mind it may raise its head again at one point. Yeah, that's. Gimme another one before The failure.

Josh Makower

Before the failure. I'd say the next the next one that is I think, gonna be a big success. And in fact, just today I was on a call with the CEO and we have won our pivotal trial, which after literally 10 years of work is a huge accomplishment.

And this is a company called Moximed, and it is a technology for earlier, early stage osteoarthritis. And so osteoarthritis, which is the calcification and degradation of the inner joint area. That, that kind of interdigitates, there's a number of places in the body where we have basically every joint.

Dr. Grant Stevens

Joints, bone to bone.

Josh Makower

Bone, it becomes bone to bone. After it, it degrades. And then lots of pain and lots of like you don't wanna move it cuz it hurts. And imagine, if it when happens in the knees or the hips, it can be debilitating and really accelerate a very poor quality of life and death ultimately because you, why would you don't wanna move.

And so this also tho that disease is also highly correlated with, addiction to opioids and, cuz you're in, so you're looking for some relief and so then people get hooked. And so it's a problem for the nation is earlier stage arthritis. And especially in younger people. So younger people being like 35 to 50, younger than me, but when it happens in younger and when you're younger, the docs will be like, I don't wanna put a new knee in you because they last about 10 years.

And then if I, if you're 35 and I put one in, now you'll be back at 45, you'll be back at 55 and your risk of death goes up every time you go for a revision. So they wanna put that off, but what do they have to offer you? And then, and literally it's pain meds.

It's it's don't work as much. Like they, you get a brace that you could wear, but that's a pain in the ass. So there really is. And they're trying things like injectables and none of those really work that well. And so we looked at it and said, okay, here's a need. You got this situation where the, again, drugs and stuff not working well, surgery way invasive, not appropriate.

What else can you offer these people? And can we do it in a way that preserves their joint and gives them, isn't as invasive? And the idea that we happened on was this idea of an external a shock absorber. that sits outside, outside of the knee, but underneath the skin. Okay.

It's implanted. So let's say on the femur anti tibia , and it creates a counter force. Right in the area where the where the, where they be touching osteoarthritis is. Pushes the bones away. And by doing that, the effect is of as if you lost, like a hundred pounds.

Okay. And when you take the pressure off, the bones can more readily heal and they hurt less. So you feel comfortable running and walking and doing all your exercise because there's a lot less force there. And the disease itself doesn't progress as much. So the idea is, so the thesis was if we put these things in, can we reduce pain?

Can we improve function and can we get long-term durability and prevent the need for and prevent the progression towards a total knee? And that was what we were proposed. And we've been working on this thing for quite some time and it's been difficult because part of the reason is that as soon as you put these things in for patients who were active, and first thing they do is they go out in their jet ski and they give it a ride.

Yeah. And we just stress it out. Hey, stress it out. And and we've had over the history of the development, too many of those things that, didn't live up to all the things that people want to do with it. So we had to go back, fix it, make it more robust, so over the time of patient's iteration to get it right.

But finally we are here with a a successful trial. And so this is coming to, this will, then navigate through the FDA process and then hopefully we'll get a straightforward approval and we'll be able to bring it to patients. But this is gonna be a revolutionary. A revolutionary technology for early stage arthritis, a mechanical solution that will reduce pain and improve function and be a great alternative to total knee replacement or some of these other therapies.

And it's gonna allow you to have your knee without a replacement and maybe never have to have a replacement depending on how the long term data stacks up. But this is a really exciting moment actually today.

Dr. Grant Stevens

Will ortho be putting it in, orthopods?

Josh Makower

Yeah. Ortho, orthopods and sports Medicine.

Dr. Grant Stevens

And sports medicine. And it's it's a kind of a distractor. It distracts bones and somewhat of a, sounds like on a car, a.

Josh Makower

Yeah, there's like a springiness. Yeah, there's a spring in there that, that adds force to distract the bones.

Dr. Grant Stevens

Is it attached to that femur and, and fibula? So it's attached to the bone, it's attached to both sides. Is the patient asleep or awake for the procedure, or can they do spinal or epidural?

Josh Makower

We have done it in where the patients are under, it just makes it easier to manipulate the joint and everything. You have to create an incision and I imagine it could be done. I, it may in fact have been done with a spinal already, but I'm not I'm not sure.

Okay. I think we've done it under general. But but still it's it's just an, it's an incision. Put the thing down.

Dr. Grant Stevens

It's a lot different than replacing your knee joint. [Yes, it is.] It's a lot better than where they cut your everything.

Josh Makower

Yeah. You get to keep your knee, your knee is still your knee. And if any time in the future you needed a total knee, you can just take this thing right out and put a total knee. We don't, we specifically designed it to leave all of the surfaces that are required to put a knee in, a total knee in available, so you can revise to a total knee in the future, but very few patients have in the trial. And so it's really been a great success so far.

Dr. Grant Stevens

Congratulations. Now, before we get to the failure, thank you. What about this vagina thing?

Josh Makower

Yeah. So we, so I so I always go in directions where everyone thinks, you can't do something. I, it's a sickness. I don't know why. No, that's, it's, yeah.

Dr. Grant Stevens

You're trying to solve problems that haven't been solved. I'm not a follow in ways that no one's ever thought. You're not a follower.

Josh Makower

I'm not a follower. I like to blaze new ground and I like to take on hard challenges. And this was one that was interesting that came across. my radar, which was, look, we have Viagra for men.

And it's all over the television and everywhere. Speaking of Pfizer, speaking of Pfizer. But what do we have for women? And basically nothing. And and so I got exposed to this need at a urology conference where I met some people that were trying to do some innovations in the space, and they were just saying unfortunately no one, no.

There haven't been a lot of credible efforts here. And what's happened is a lot of the things have found being sex toys or things like that. But no one's actually brought any real science and nobody of any, I would, I shouldn't say nobody, it's been difficult for, I, there haven't been very few people with medical credibility that have actually, stepped forward and but there was evolving to be, and so there's a whole specialty on sexual medicine, and these folks are champions for this need.

But on the corporate side, I think that, so there were definitely champions on the doctor's side, but on the corporate side, the, there was a squeamishness, VCs are primarily male. This is, we don't want to go here. Of course they can back Viagra, but when it comes to something for women, it's Ooh, I'm not so sure.

And then they're, they're afraid of it being porn or something like that. And then and then on the corporate side, same thing. There's this, there's a real insecurity over women's sexual health, whereas there seems to be broad acceptance of men's sexual health. But on the women's side, it was different.

And I just thought, this is a social challenge and it's a technology and medical challenge. And then, and so we working with a number of great physicians Dr. Leah Mill, Heiser, Irving Goldstein down here in Southern California, and really top thought, thought leaders across across the country.

Came to understand what the physiology is and then developed a device that we believed would produce a Viagra like effect for women. And we were able to get adventure funded. I was of course affiliated with the, one of the VCs that led the way. And we took this on not only as a device for women, but also as a social change opportunity. And that was a hard project too.

Dr. Grant Stevens

And did this go through FDA approval?

Josh Makower

It didn't have to. So our claims, so we did not need, because of the claims that we wanted to make, which was essentially an arousal claim, those are not regulated.

Okay. So we were able to introduce it as a sort of an arousal device. For women. And yeah, but the pr the interesting problem, the reason why the company struggled was not because of the technology didn't work or anything. We did do clinical studies. It was very effective. It the idea of it was you used this for, a couple minutes and that promotes these feelings of arousal, which then have both a stimulatory effect, a blood flow effect, and then of course, even psychological effect of promoting an interest.

Which women, you say why we don't have permissive who is this for? Men, no women. Some, there are some women who wish that they had this dis feeling desire, but don't and don't know how to get it. And actually this device which, basically promoted blood flow essentially provokes a feeling of interest.

It just does. So the problem was that Google and Facebook wouldn't allow us to be promoted on their platforms because it had to do with sex. They, and they said, oh, go over the porn side of the business, but you can't promote on any legitimate platform. We're like whoa. Wait a second.

No. We're separating ourselves from that. Look at our advisory board, you've met some of these folks. They're, this is like the world class advisors in the space. Like we have clinical data. We are not gonna be over here on the porn side. We wanna de-stigmatize it. And make it like, Viagra for men and no, we couldn't.

So when you, they are the platform online. You cannot advertise anything online without access to Google and Facebook's. Platform. How do you get any word out? How do you communicate with people? You can't? So we were basically censored and we had a campaign called like Legalized v that was not my idea.

That was Karen Long's idea. Of course, Karen? And and Dr. Mil Hodge's idea, and they basically, we ba they, they basically picketed out in front of these saying You'll legalize me. But and we did get a little bit of, movement, but it was too little, too late at that point, I think we just ran outta gas and we couldn't, it was hard to convince people that there was a real opportunity there.

So we did wind up selling the business. It wasn't a. failure. We sold the two business that was in the businesses. Sexual health had a bunch of other drugs and it fit with their portfolio, but but it wasn't what we dreamed. Is it being used today? I think so. Every now and then we do get a call for some of the refills.

Like I would say we, we redirect them to the, but it's not a big, it's not the big oppor. Generally we try to take on big opportunities. That are gonna be like billion dollar, millions of patients type thing. That's definitely not that.

Dr. Grant Stevens

And what's it good, what's the name now in this new company?

Josh Makower

The company that bought it was Aytu, A Y T U, which is a small company in Colorado that has a number of like testosterone and a couple of other things like that. And the device is called, the device is called Newell's. Newell was the name of the company. The device was called Fiera.

Dr. Grant Stevens

So there are all maybe we're relaunching it right here on the technology of beauty. It could be maybe a spinoff, of technology of sexual awareness and arousal. That's right. Okay, there we go. Now, problem after problem now. Tell us about the one that you went after. And you call a failure.

Josh Makower

Oh, sure. That was targeting obesity, that was definitely the.

Dr. Grant Stevens

What he said was targeting obesity. Now listen to this.

Josh Makower

At the time we were, just going back at that time, there were like 30 different companies that were, that were thinking of ways of treating obesity.

All lot of implants, lap band was the target, like lap band was really taken off. And surgery was really metabolically successful, but, Very difficult for patients to deal with. And so we just saw, again, this situation, big and bad, invasive surgery, some minimally invasive things that are working, but maybe they could be better.

And we, and the primary thing we were handling in on is this lap bands are so sensitive, like they can erode so, so easily and they have to be adjusted all the time. And it's a big deal. And Lap Band, by the way, is a band that goes around the stomach that basically compresses your ability to eat.

So it, it's a restriction technology and and it's, it was finicky. It was successful but very finicky. And so we thought, can we make something better? And so what we developed was a balloon that was the size of a stomach that would sit alongside the stomach and expand and fill the space that the stomach would normally expand into.

So the feeling of it would be that your stomach was, that you were full. Sure. So when you feel full, you don't feel like eating. And of course, mechanically, you didn't have a lot of space in your stomach left because all that space under here was being filled by an eggplant shaped balloon.

And and also nice thing about a big egg, eggplant shaped balloon is it's a big broad, soft silicone thing. There's no points of no high points of force erosion. So you really didn't see any erosions and really dress the erosion issue. And of course it was also very adjustable because it's so big, you could take out, you, you're not like dealing with a difference of a millimeter like you were at the lap band.

It's this big broad structure. You can be very, it can be very forgiving to small differences. And It was more physiologic, potentially.

Dr. Grant Stevens

Was it full of water or saline or air? Air?

Josh Makower

It was full of saline. Saline, saline had to be full of saline because air would be like this, like a water balloon under, if you went on, you.

Dr. Grant Stevens

And how would you access it? Through a port?

Josh Makower

Through a port. Yeah, through a port that we put on the.

Dr. Grant Stevens

And how would it get intraabdominal?

Josh Makower

We had a small laparoscopic insertion. The whole device would get the thing in there, and then we would actually, there was a way to attach it to the anterior abdominal wall. And that fixated it in place. And then you could adjust it, close it. Leave a port there.

Dr. Grant Stevens

Just a small, just like tissue expanders for the rest.

Josh Makower

Like a tissue expander. Exactly like that.

Dr. Grant Stevens

Sounds like a tissue expander.

Josh Makower

And that company did fail. And I'll tell you the moment that I realized that I felt, we had a failure on our hands because we were doing the clinical trial and we probably enrolled about 200 patients. And it was the weirdest thing. We had some patients that were total rock stars. Like they lost all their, we they looked amazing.

They were happy. They were, they the absolute success stories. And then you had another group of patients that didn't lose any weight at all. We adjust their implants up and adjust their implants more or just, and they were just not losing any weight. And of course, on average, when you average those two bifurcated groups, it's a good result.

It was basically equivalent to a lap band. And we always commit ourselves like if we're only gonna be as good as existing prevailing thing, we're not gonna do this. I'm not, I don't wanna, me too, I want a better, it's gotta be better. And if it's better, then we're gonna do it.

If it's not better, then we're just not gonna, it's not worth it. So it was not that much better and we just couldn't figure out if we could just be these rockstar people, it would be blissfully amazingly better. But why were half the patients in this not changing group? And I was surfing online and found a YouTube from one of our patients who is talking about the implant now.

They were in the middle of a clinical trial and they're not allowed to do this. They're supposed to actually keep confidentiality and so on, but there she is. She's talking about, the implant on the YouTube and I'm, this goes like this. She's, I'm so very still clearly overweight woman.

I'm very thankful to the vibrant implant. so thankful. Cause you know, I used to just sit down and eat a, eat a whole pie, for Oh, just like over lunch, and now it takes me four hours. Bottom line is the pie's going in. The pie's going in. And it doesn't.

Dr. Grant Stevens

So the caloric consumption was equal. It just took 'em longer to do it.

Josh Makower

So it wasn't what the recogni, the failure there. That is, that it's just, it's not here. It's here. That's what it's here. It's here. It's it's it's your, it's, this desire to eat, you could feel as full as possible, but the desire to eat is not about having an empty stomach and feeling hungry. It's about satisfying some other need that's more psychological and that we weren't addressing. And that's why, half of our patients did not lose any weight.

Dr. Grant Stevens

But what's clear to me, and I've heard this story before, is there is still a subset of motivated patients who could use this technology. And successfully drop weight.

Josh Makower

Oh no. It worked. It worked for them. It worked. But it's.

Dr. Grant Stevens

If you could separate those, if you could vet them. If you could figure it out, figure, figure out who's gonna be a.

Josh Makower

You know what, the thing is, and you know this Grant, cuz you've worked with so many companies, you only get a chance to get it right once.

Because the VCs, and I'm a vc, and I get it. It's like after you spent all this money, they don't want to hear okay, now we've got it. No. You're done. And could we have, I guess if I thought, there was a logical way to figure out who's who. Then I might have said, give us this chance, cuz I've done that before.

I've gone back and said, no, I believe Nere, the urology one. We had a lot of challenges and I went back and I said no, believe me. And my mentor and board member at the time, John Nira went back to him and he was like, you want me to write another check for this?

Cause we were having a lot of challenge with the FDA at the time and I said, John, I really believe in this thing. Give us the chance. And he was like, okay I'm backing you. You believe in it. This, in this case. I felt the reason why we let it go was I just felt like I knew, I wasn't really addressing the issue.

Noom is more successful than Noom was. The right is the right solution. To this problem. It's here. It isn't about trying to. turn the stomach into the tiny little pencil tube, and so that's why I, yes, you're right. We could have gone back and tried to do a better job of and get there eventually, but for me, what gets me outta bed in the morning is doing something that I know really is the right solution rather than just, making something be okay. I want something to be, I wanna do great stuff. I don't wanna do so-so good stuff.

Dr. Grant Stevens

Now we've gone through a number of problems that you've solved. And you've worked on, you are a doctor by training. Not a single one of these problems falls into pure aesthetics. And the two problems that continue to affect us in aesthetics, there are a number Yeah.

But one is stretch marks and the other pressing one affects pretty much every woman on the planet earth. And that is cellulite. And you and I had worked together on ais before I got the call from you. And had the wonderful opportunity to start working with you and your engineers.

Thanks. And the various cadavers and the labs and all the rest. What a wonderful, it's good ride. Wonderful adventure. It's been a been, and I've enjoyed every sur every mor level. You're amazing. Great partner. You identified this problem. That it affects, 90% of women Yeah.

That are post pubescent. And that's cellulite. And you said, okay, yeah, we're gonna go after that. And of course, the first thing I see, Is a balloon. You see the theme here?

Josh Makower

This is the first idea. The first idea.

Dr. Grant Stevens

I trust. Trust me, it's not a balloon anymore, but I thought that was so funny that you start chasing cellulite with balloons. [We did. We tried it.] And engineers who they were used to making little tiny balloons, open up vessels and prostates or whatever, and out that came a new technology. That has been FDA approved. Why don't you share that, which you'd like to. Our CEO is going to be on also. But go ahead and tell us a little bit about NC- eight,

Josh Makower

Now called Revelle Aesthetics.

Dr. Grant Stevens

But NC-eight was what we called it and that was New Company eight.

Josh Makower

We could, we number all the companies so that the name doesn't give away what it is. So he can remain stealth as long as possible.

Yes. And in this case, we've remained stealth all the way up until product launch, which will be this year, which is exciting. And I do want to thank you, grant, for all your guidance and your tremendous input and perseverance with us because as you pointed out, the first idea didn't work.

And we went into the clinic and we tested it, and we didn't like the results. And back to what we talked about, we're not just going to push something that doesn't really work that well, we want to go find the thing that kills this thing that really does it. And it's important. We spend so much of our lives working on this kind of stuff.

it doesn't make any sense to do stuff that's just you really wanna do something that makes a difference. And I committed myself. I've looked at aesthetics many times, many other areas, and I didn't, I'd never done anything in aesthetics before because I always felt like the results, like if I can't, if I can't tell the results better , I just, I can't get into it for this.

I, this was a difference maker for me. And our goal was to do something that when you look at it, there's no doubt even the biggest skeptic, you can't, you, if you see it, you see a big difference. And that's what we were going for. And the idea was the, I'd say the under the opportunity is, there was a historical technology, which is pretty much off the market now called Cellfina.

that I know you had a big role in, in creating, and they got a lot of stuff. Which was that cellulite is the, where these subcutaneous, fibers, we call 'em septa, are non uniformly distributed across the subcutaneous domain between the fascia and the and the skin that sort of hold your skin to your body.

And when they're irregularly distributed, that's fine if they all stretch the same way. But if there's a bundle that has a little bit more girth to it and it's not as stretchy when gravity acts on the. that area doesn't move down with the rest of the skin and basically creates this appearance of a dimple, which is essentially like a puppeteer holding back that part of the skin with a fiber.

And so Cellfina got it right by saying, Hey, no, let's go in and chop those fibers. But what they didn't have a way of doing is being discriminatory about what fibers they were cutting. So they had to cut a broad, they had to cut the forest down to get that one or two trees that, that they really wanted to go for.

And that resulted in more bruising and subcutaneous bleeding. And also trauma that really resulted in not a great patient experience for many people. And so the idea. Of what we want to do is say the fiber idea was the right idea, but how do we do it in a way that is more targeted and just gets the fibers of interest rather than these techniques and technologies that sort of broadly apply, what have an energy or mechanical disruption across a broader area can, and even drugs.

Can we be more focused? Can we be more focal and just get that structure where it is? And so we introduced into the clinic. First we thought we could do with the balloon and we thought if we could just put a balloon right nearby, we could blow up the balloon and stretch it enough, it would pop.

And that's, that failed. But what we learned about that was something that was really also a reason perhaps why SEN would, may not have been as effective is that these fibers. are very stretchy. We've worked in the lab together on this in cadavers and observe that you can hang on one of these fires and just pull and pull and pull and stretch and stretch.

And so when you're trying to think about, your Thanksgiving dinner and the Turkey there and even though you have the sharpest blade coming at the Turkey, you know from the side that turkey's just gonna move right across the table. So even if you're, doing this sort of broad cutting technique, you have a chance for those fibers probably to be escaping on either edge of that treatment.

So the idea that we came up with, and that's it. Give credit to the team. There's a, any of these, by the way, I wanna just make sure I give credit. I am not a individual inventor. I always invent with a team, so there's different team you've met. At Bright John Podmore, we did this together and observe that that basically if you could just grab that fiber and then test if it's the one.

So you grab it, pull on it, and if you can recreate that dimple in the spot where you know the dimple is. Then you know you've got the fiber of interest and just zap that one, just cut that one. Then you can minimize your trauma just to that fiber. And you don't have the broad bleeding, you don't have the broad dis distribution of of bruising, et cetera.

And it can really be focal about it. And also you give the back to this engagement of physicians. Now physicians can go like a, targeted system. That one. And just go for those rather than, a broader distributed approach. And this can really have the potential of being dramatic and instantaneous.

And as we both have observed, the power of this is literally these patients stand up even in, in the middle of the case and you can see it's gone, we took the string away. I really think that this technique which is a product now that product's name is gonna be called Ava Lee.

And we're just introducing it this this month. But I really think this this is going to transform the treatment for cellulite. And I Thank you Grant for, your excellent leadership and guidance and feedback and encouragement and challenges. along the way. But it's been a great partnership and really it's been a pleasure.

Dr. Grant Stevens

So thank you. It's been a lot of fun. Before we move on to Stanford I also wanna point out something else to the watch, to the listeners and watchers. So in addition to the ability to identify that one, as he said called it a thread, fiber, whatever you want to call it. The other thing we learned is that oftentimes there isn't one.

There may be one main one, but then it may bifurcate or trifurcate. And when one gets the one, the tendency is then to say, I did it. I got it. But uniquely what this allows is pointed out by Amanda and some other people who watched every move I made and videotaped it. And analyzed it and showed me how to do a better job.

And then we looked with endoscopes. There are oftentimes this bifurcation, trifurcation, and so forth that would come up to the skin. We'd go back a second or third or fourth time and hook yet another fiber. So in addition to the precision of getting the one and not undermining the whole buttocks, the other advantage is the isolation of any other collateral fibers.

Which is an extension of what we learned initially. And that's equally important. So the precision, absolutely. But also the identification of the other ones, because I think that's what led to the early failures of many of the technologies is physicians such as myself and the people doing the therapy would rejoice mentally.

They'd say, I got it. And there was that feeling of success and it was right. But we didn't think about might there be another one? Or a collateral one, like a branch off of a tree. And it was when Amanda came down a few times and showed me. Boy she's tough.

Josh Makower

And Amanda White, one of my fellows from Stanford.

Dr. Grant Stevens

Yeah. And I look at it, I'm like, golly, because she broke down when I was successful and I wasn't. And it was that rigorous time motion studies in her precise watching these tapes. And pointed out to me and Absolutely. I know initially as the surgeon a very. Successful, accomplished experience surgeon having this, Stu, your graduate student, tell me that I wasn't doing it right.

I was like, I'm sorry, but you know what, she was absolutely right. And when I changed my technique, it worked and so forth. That's a credit to you Grant. It's a credit to Amanda and to the whole, and the whole team. And the team has been

Josh Makower

Caro's an amazing leader, Caro Van Hove, amazing leader.

Dr. Grant Stevens

And I, she's building a fantastic, I'm not even sure how much I can tell you, but I'll try this and see if this stays in. This included multiple cadavers as we had to get it right. And included even cadavers coming to my or and videotaping and so forth. And hopefully that doesn't get cut.

Yes. But yeah, there was been a lot of fun. It's over years and then, and also going out of the country with Craig and so forth. And we just completed 77, I think, people. FDA approval and commercialization. And I couldn't be more excited. Thank you. Me too. But I want to go on, cuz you mentioned Emmanuel, would you please share with all of our viewers your position at Stanford?

That little college somewhere in the Bay area? The department, your position. Yeah, your chairmanship. So I think that's germane to this whole Thanks. Wonderful story.

Josh Makower

Thank you. Thanks so much. As this technique of finding needs and solving problems is universal to use to any medical issue the desire to share that with others and really train innovators to do what we do is really central to me as well, because I'm only gonna be able to help so many people.

But if we can train others to do the same thing, then, we can make a big impact. And so 20 plus years ago I teamed up with Dr. Paul Yock. And Paul Yock is a famous intro cardiovascular, interventionalist. And and we basically started Stanford biodesign with the goal of training innovators in this methodology.

The need finding thing, all the stakeholders go through the sort of identification, need specification, there's this rigor, and we began with just a small four-person fellowship, a year long fellowship. And then and then a corresponding graduate class at Stanford. I was, came on as an adjunct and have worked in for the first five or six years.

I was the fellowship director there, actually ran that innovation program, and then my startups were just becoming too. I'm too busy and I went to more of an advisory and more mentor role with the fellows over all these years. But most re so now 20 years later, the program is massive. We have like probably touch, 12 full-time fellows that are our plus global fellows and faculty fellows and our program, we've written a textbook and so we're on our second edition.

And the teaching is being, and the biodesign programs are spread across the world. And there's programs in literally almost every country in the world and many of the states that any place that has a bioengineering program, has a program like this that may use our textbook. And and so this idea of this sort of structured innovation approach is really taken off.

It is a simple idea. It's. It's not rocket science, but sometimes simple things really stick, that's right. And and so we are sitting here now, 20 years later with this massive program and international influence. And my co-founder Paul, is, gonna retire. And so the ask was, would I be interested in coming back and running it now?

And at first, I was I've been a general partner at nea, managing the medical technology investing practice. But this was an opportunity that I just couldn't say no to. And as I think about like the back nine of my career , to be able to, take a more direct and active role in shaping the future for biodesign and setting it up for long-term success and sustainability.

And that was a, that felt like the right thing to do. So now I'm a professor at Stanford. and med appointed in medicine and bioengineering, and I'm the director of Stanford Biodesign, and I'm charged with charting the future of what's next.

Dr. Grant Stevens

And that's cool. And that brings me my next question. What is next? What is next? What? You have a crystal ball. I heard you brought it with you. Did you bring it down? I, I think it's, tell me where, tell me what 1 3 5 10, what's the future look like?

Josh Makower

So the future the future for biodesign will be that, as I'm a device person, but really today the innovations are everywhere.

Biotech is huge. So we're gonna re dimension biodesign to be all life sciences. So it's already happening. There are already are biotech companies and pharma companies and digital health companies that, that ha that our students and fellows have created using our approach. But we're actually gonna reinforce that and double down and make all life sciences for biodesign.

So we're gonna broaden out. So in the future, We'll have people creating the next mRNA vaccine or whatever it is or whatever idea it is that using bio technologies or whatever it is to solve problems rather than narrow to medical device. That's number one. Second, second one is to create a policy program.

We're gonna, we're gonna actually create a full-on policy program at Stanford, which will be focused on innovation policy to bring, to train policy makers to go into staffing positions in Congress and the White House, and understand how technology, especially medical technology is evolved so they, they can better create laws and policies that enhance the ability of medical innovation rather than defeat it.

And then the last one is last thread. The new thread at Biodesign is to really refocus our international and external efforts on really underrepresented and under Under resourced parts of the world. And that includes right in our backyard here in the United States, but also internationally.

And use our techniques to help those communities, get the healthcare that they deserve, but have it be the right si type of healthcare for their needs and their environment, rather than trying to push, whatever's whatever's coming from other places without the same need set.

So that's, those are the three things that we're doing for biodesign and yeah, so that's the future for Biodesign.

Dr. Grant Stevens

Fantastic. It's been a fabulous thank you time getting to know you better, Josh, and I'm sure all of you have had a wonderful time getting to know Josh. I want to thank you so much.

Thank you for coming down, making time in your busy schedule. You've got a million things going. Thank you. You're one of the busiest guys. I know we're pretty busy thanks for coming and sharing this time. I appreciate thanks us and the viewers and the listeners and look forward to seeing you. Yeah.

As we co-chair various things like AIS and chase some more problems together and solve some more problems. Absolutely. [Thanks Grant.] Thank you Josh. Appreciate it. So there you have it. Thank you all very much for joining us on this episode of the Technology of Beauty, where I have the opportunity to interview the movers and the shakers of the beauty business.

And you just heard from one of the biggest movers and shakers of all biodesign. The chairman, the head guy at nea, and my partner at NC-8 and Revelle. Thanks. See you soon. Stay well. Bye-bye.