Why a Device and Biologic Combination Product is a Challenge and an Opportunity
Patricia Zilliox has devoted her career to solving problems with the eyes. She had a very successful career at Alcon, then at the Foundation Fighting Blindness Clinical Research Institute, before joining Eyevensys as CEO. Eyevensys is working on a technology that has the potential to solve a big problem. In this episode Patricia shares how a biologics company approaches device design and manufacture, combination product development, the regulatory pathway, funding challenges, how device differs but is similar to pharma and biologics, and how great companies retain great people.
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Episode Transcript
This transcript was generated using an automated transcription service and is minimally edited. Please forgive the mistakes contained within it.
Patrick Kothe 00:30
Welcome! If an entrepreneur had an idea for a new type of car, that entrepreneur and the investors would be able to identify the market opportunity, the risks, put together a timeline, make financial projections, and then project a return on the investment. And if somebody had a new type of airplane, the same thing would be true. And the reason is that entrepreneurs and investors have experience with similar types of projects. And they can make reasonable assumptions reasonable, reasonable projections, they can assess what the risks are, and then manage expectations. Now I want you to imagine somebody that had an idea for a flying car. People know about airplanes, they know about cars, but who know not so much about flying cars. So people's confidence in the projections and expectations and risks will be much different because there isn't a previous previous path for a flying car. And now in many ways that's similar to what we're going to talk about today. And that's a combination medical product that combines a medical device with a pharmaceutical or biologic agent. Patricia Zilliox is my guest today and she's developing one of these combo products. But Patricia has devoted her career to solving problems with the eyes, and she had a very successful career at Alcon. Then at the Foundation Fighting Blindness Clinical Research Institute, before joining Eyevensys, her current company as CEO. Now events this is working on a technology that has the potential to solve a big clinical problem. However, she's also navigating some big challenges. In our conversation, we discuss how a biologics company approaches device design and manufacture, combination product development, the regulatory pathway for such devices, funding challenges, and then how a device differs and is quite similar to pharma and biologics. And that we also discuss how great companies retain great people. Here's our conversation. Patricia, welcome. It is so great to have you here. Join us here today.
Patricia Zilliox 03:11
Good afternoon, like thank you for having me. I appreciate
Patrick Kothe 03:14
Patricia, most of our listeners are in the medical device side of things and you've been in pharma for for your career. I started off in pharma and found that I gravitated towards the device side of things. But you spent all your career there, what drew you to Pharma? And if you can kind of give us a little bit of a history on you know, what types of companies what types of roles that you that you had within Pharma.
Patricia Zilliox 03:41
So what did attract me to pharma, I haven't found the degree to start to begin, but I had to do him. I always wanted to develop drug. I had an uncle where the pharmacy shop, I like the ripping dog. And I always wanted to come to United States because for me, it was a country where we American walked on the moon. So I thought there was something magic about you guys here. So I joined initially, my first experience was in a small company, a French company in France in East of France. And they were developing eyedrops for a disease. And it was great, but it was not accomplishing all my dreams. And very quickly after I joined the company, it was acquired by Alcon I'll go in photos. I didn't know what fault was was on a map, I have to admit. And very quickly I took the opportunity to, to to be transferred here to headquarter. And I grew up in that company for all my career for 25 years. So it for me it was accomplishing to dream of being able to do have developed drugs and being a United States because I've really felt there was some magic about here. So that's how I arrived here. Duncan,
Patrick Kothe 05:01
being here for 30 years or so now, is it what you expected it to be? Or, or is this us different than what your expectations were?
Patricia Zilliox 05:11
I love it. i It's 24 years. 23 years actually. I love it. It's everything I wanted to know. It's I love the way people work. People work hard. They work in teams, the focus. I like the work ethics here. I like the collaboration. People get things down. And I don't think the American people realize how great country it is here is a look at ways ways. With focus, they teamwork. It's not always perfect. I realize that. But it's what I wanted. And it's what I expected that I'm still here.
Patrick Kothe 05:50
So within Alcon what roles did you did you have? What part of the business were you involved in?
Patricia Zilliox 06:00
So I was always in clinical I started in clinical trials, I started with Marcus riposte. While and when I grew up in the organization, in Vietnam, mainly, I started the first project, I was working in retinal diseases. I'm not talking about surgery, I'm talking about drugs. And I grew up in the organization when I left in 2011. At that time, Novartis was there, I was head of clinical ophthalmology. So I never would direct in devices, I was involved with devices because of drug delivery systems. But I was never involved in the development of device per se. So I was really, you know, the pharma division.
Patrick Kothe 06:42
So spending, you know, 2324 years at Alcon that's a substantial amount of of your career, such a substantial amount of time, I always find it fascinating. Some people are, you know, two, three years with a company and then moving on to the next one, or five or six years, but a long, extended period of time with a company can be unique. So how do you look back at that portion of your career and say, What kept you motivated, what kept you driving after you've been at the company for that amount of time.
Patricia Zilliox 07:16
So what kept me there was really, it was an awesome company. A loss of management area management wanted to mentor people. And they there was a management in place at that time, wanted to keep people for a long time. So there was a lot of mentoring and growing. And the other thing too, there was opportunity. I wanted to grow the organization, I was given the opportunity to grow. It was not like, you know, I was in a box. And one is, you know, I come was sold to Novartis I stayed two years with Novartis and I left Novartis in 2011. Because it was very silo. And I didn't like that at Alcon the organization was really, we everybody was involved in the big picture. It was our company. And it was a company of technologies, we had a very, very close relationship with ophthalmologists, who are the customer of the sea. And I think that's where a lot of people like me stayed for very long, very protective management, very mentoring, a very global approach at every level of the organization, and very close with the ophthalmologist. But I think that was that Martinez, which makes us stay with a company.
Patrick Kothe 08:36
So the the culture of the company and how they treated the employees, but also, we all we all have times in our career where we want to grow, we want to do ever do other things as well. So they provided you opportunities to grow and to challenge yourself and work on challenging projects as well.
Patricia Zilliox 08:54
When you have a thing to think about. I'm a French citizen with a French accent. So educated in France. They accepted me here but give me responsibilities. On top of that I was a female coming from a country very chauvinistic. I mean, what can you do more? I mean, I got everything you hear. So I really enjoyed it.
Patrick Kothe 09:16
That's great. And talent wins. Talent always wins. So that's great. That was recognized and you had had a great opportunity there. So let's talk about you know, post elocon. And I want to get to the company that you're leading right now. Ivan says, so can you tell us a little bit about you know, how you got involved with AI Ventus and what the mission is of the company.
Patricia Zilliox 09:40
So basically in between Ivan's is an icon actually. So there's something which is called Foundation Fighting Blindness. And when I left in 2011, Novartis, that's what I want. I want to Foundation Fighting Blindness. I cannot go enough technology because Novartis was not very happy when I left and begin noncompete for five years, and I joined this organization in Washington, DC, and it was absolutely awesome. So what was awesome about that organization, it's a foundational research foundation. And their mission is really to find treatment for a disease due to gene mutation, kids who are getting blind. And my contribution of a ver was really about the outcome per show of avail the way of thinking of drug development. And we did awesome thing of avail. Just as an example, when I joined in 2011, there was one clinical trial for P. Today, well about 300 clinical trials going on for P. And I can guarantee you that I don't think there's any single study welcome, predation, fighting binders in the heavier hands in it. Revision of Mr. Gun was absolutely amazing. And so what what I do my horrible there was really over where to work on clinical endpoints try to help company to be creative, so we can develop Dr. So treatment for this disease. And it's while I was doing that, we created a company in Paris. And that's how I met investor we introduced me to identities. Why did I leave foundation? Why did I join agencies? I love I was very, very intrigued by the technology of five MCs it was different was the device, two devices, a plasmid, it was very much into it without the virus. So it was something I knew there was a medical need, there was something I knew would be accepted by the ophthalmologist when you talk about marketing and how we're going to market this, this approach. I knew there that there was a need for the market. I knew it would be difficult. And at the same time for personal reason I mentioned before, I wanted to get closer to my father in France. So this was an opportunity for me too. And I think I had done what I could do for Foundation Fighting Blindness. I had done what I wanted, as I said, there was one or two there are 300 trial, I did bring all my my expertise to them. It was now time to move on. So I don't even exist because of technology first. Second, because I think I could bring something from Alcon and also from Foundation, or we don't want to underestimate Foundation, as well. Does it make sense?
Patrick Kothe 12:15
Yeah, absolutely. So the the challenge that you're trying to solve what what is the, the issue that you're the clinical issue that you're trying to solve?
Patricia Zilliox 12:27
So today, when you treat the eye disease of the retina, there's one key disease which is called age related macular degeneration. And the two forms what form in the dry form, the wet form they are, they are treatment available, which are called NT budget recentes er you probably heard about, they do require an injection in VI directly every month, every month, every two months. Your elderly patients are generally 7080 years old, they have to go to a clinical office and get a shot in VI every single month in both eyes. But it is a leading cause of blindness. I'm sure you have a brand mobile around you who was affected by the disease. And you probably realize that in the last two years going to practice every month for shutting VI was not something feasible. So as a consequence, lack of compliance, patient lose vision, it doesn't work, and you can try to treat. So I knew we were technology while developing we can avoid that need to inject every month, I know that we can come back and when checked every six months or maybe every year. So here we're going to make a difference of a patient. The Second Indication we're also targeting is dry empty, which is the dry form of macular degeneration. There is no treatment available today. These are patients they have accumulation of drusen type of debris in the retina, they coalesce together. And then the you have what we call geographic atrophy, this vision become big, and patient gets totally blind. And today is no treatment. And they are some treatment developed with some some pharmacological approach, which again, we do require a shot in the eye every month. And here again, our proposal is weekend we believe we can slow down progression of disease prevent this patient to get totally blind by not injecting them every month but maybe every six months or a year. So this is a secondary I can we can really make a difference. The third area is when you talk about gene therapy. What is gene therapy take plasmid like we do that you put them in a virus and then it's permanent there. It's going to probably work finally does work because there's one treatment of poor which is called Sparky 65 which is one type of mutation for P. It works but it's there for permanently. So once again, if you have kids who are getting blind and you want to edit the gene mutation or open the gene mutation, gene therapy with a virus can make a difference. But if you think about elderly people, if you want to stop it, you can't anymore. And we know today with viruses in injected in VI, well, some immune reaction and therefore some side effects. So for good reason why I believe in this technology, when I believe we can make a difference, even if it's tough to develop, even if you have device, I know we can make a difference.
Patrick Kothe 15:29
So we've got a kind of a combination device here, there'll be a device and a pharmaceutical, let's just focus on the pharmaceutical for a second. And I want to I don't want to get too deep into it. But what's the mechanism of action? How does this pharmaceutical change the progression of the disease?
Patricia Zilliox 15:47
So first of all, I need to correct you it's not a pharmaceutical incident biologics. So it's a big difference, not the same division that the FDA, it's not a chemical edge, and it's a plasmid, I'm sure you remember your courses in high school plasmid, you encode the plasmid to produce a therapeutic protein, so protein that you produce another chemical. And what we do here, or both, we take this plasmid, we inject them one big on the scenery must always a cartoon on website that explains it very well. If you do that, nothing will happen. So you come with the divine second device, which is bulletproof transfection. And basically, you do read a hole into cell of a sphere in my soul, the plasma until the ciliary muscles, and then machinery will take over and you'll see during muscle will become a little bio factory, producing protein, directly individuals and in record, very important because that's what you want. And voila, you're done. So what we did, we developed two devices when which is to inject or our to inject exactly when we need to, which is leading to a little pulse generator, which is going to do with electro transfection. That's how it works. So very creative. By the same token, very simple. But it is about at the end of the day, it's going to be a biologic, it's not going to be a medical device, we, we have to obey to the medical device regulation, but it's still biology.
Patrick Kothe 17:16
So if I'm a medical device company, and I really don't have any expertise in biologics, I'm going to go out and search for somebody who has an expertise. So when as a biologics company, you don't have the expertise in in medical device. How did you approach you know that you needed a device? How did you approach the development of the device? Is that something that you INSOURCE people, or do you outsource the development of this?
Patricia Zilliox 17:46
So in this situation, I am by John the company as CEO only three and a half years ago. So there was already a device which was developed. And the wave of founder was an ophthalmologist in Paris, the way we did it, she is herself, an ophthalmologist, she worked with a small medical device company in Paris, these are garage companies, I would say. And they started to create from scratch, they also had to put the IP, and they started to work in animals, of course, and then slowly go in bigger animals so it can go in human. What we have done since I joined, we had to go in human of course to make sure we can do it. And there's a regulation from the FDA from the European agency which says you have to collect information to optimize the design. So what we have done we have surrounding ourselves with experts in medical devices, as well as ophthalmologist ophthalmologist who likes devices you want surgeon you don't want your often oh geez will prescribe you eyedrops, you want somebody who actually does surgery with us to do this type of things. We can help you to design the device. That's what we did. And we collected what we call user feedback. And then we tested it anymore, in big animals, and in clinical trials, and that's where we are today. So you're right. It's different.
Patrick Kothe 19:08
So when I hear about customer discovery, it's to me it's it's different depending on the type of device or type of product that you have. I would not feel comfortable going into the biologic space. I wouldn't think that I had to have the expertise in the area to to gain from the customer what that you know, what that biologics biologic would need need to do? Did you run into the same thing on the device side where you you were trying to understand the language of device and the language of the needs of the surgeons. And while you're identifying what the needs of that product were supposed to be? Was that something that you guys worked out? Or is that something that you relied on your partners who are developing the device to do?
Patricia Zilliox 19:58
No, we we did I will say, first of all on the boundary call when you were doing on the device about we went, we have an engineer in house who help us to design. And we partner with experts in the field here in United States. And we manufacture. So we went to get that expertise. And as you know, on the device, you need multiple expertise, especially here we have two devices. And each time he does develop something, we had to test in animal models to make sure that Mercedes is going to do what it's supposed to do. So we really partner with a lot of different engineer. And we both know we've often emojis surgeon who have experienced in devices on the boundary competencies here because that's our expertise. Same thing for pharmaceutical, by the way, you know, you put pharmacologists and toxicologists in dilemma. When I do what they have to do that when it comes to device, as you know, who is the user, it's the surgeon. So it was very important to have a partnership. How did I do that? Remember, I came from Alcon we did devices. So that's something I knew how to do.
Patrick Kothe 21:08
So combination devices, there may be a device that is designed in certain way, which may affect the performance of the biologics. So how did you manage the program because the biologics may be slightly changed, or the device may be slightly changed, which could affect the usability of the technology? Like that combination? So did you have a team that was involved with this? Or did you have one team on the on the device side, another team on a biologic side?
Patricia Zilliox 21:41
So that's an excellent question. So actually, only one team. So we had two teams, but not device biology. We had team at the University with a founder, and we are the team in the lab. And you are absolutely right. The challenge was to find the amount of plasmid you inject the ciliary muscle, and the electro pulse generation what's going to be the posts that you want to administer to get the best outcome in terms of production of protein. There is a team of preclinical people vouches for closely with engineer, and they tried and tried it in multiple animals, until they found the best combination amounts set injected in the ciliary muscle, they are specific to transfection that has been mobilized based on the size of the ciliary muscle and the eye of humans, it was modernized to grow in big animals, and then we will be turning old obviously. And that's what we did. But it was a combination of both together. And it started in small animals. Of course,
Patrick Kothe 22:48
when you're designing this and developing this combo product, what are some of your just from the design standpoint, development standpoint? What are some of the other challenges that that you've run into? And how do you? How do you get to resolution to some of these things
Patricia Zilliox 23:04
that are on the device, tons of tons of issues. The first one is obviously the design trying to find the right bar major IP, you have to protect your IP every single day to make because this is the heart of a business, the IP, IP, IP, and then based regulation, as you know, and I'm sure you're gonna smile at that. But when you do when you have expertise in medical device, you work with organization with quality system in place who have no via SOPs, then train everybody. We were about equal Well, a bunch of biologists so a quality system when I arrived in Barry's routine didn't know what it was. So here we had to hire the company in Denver to put in place for us quality system. SOPs were productivity validation. That was a challenge, easy to do for somebody who knows what medical devices, but have a bunch of biologies to, you know, use to mix things together. That didn't work for devices. So that was a big learning curve and an expensive one too. So we had to beef up the organization to meet the regulation.
Patrick Kothe 24:17
So these experts that you hired on the device side of things are you partnered with on a device side of things? Are they going to be manufacturing those devices? Are you going to take over the manufacturing, they're doing the design side?
Patricia Zilliox 24:29
So here Twitter be complex, we started to work with small team in Paris, one small team for the former electrical generator, and another team in East of France and those also for the Fabio pro device. And we had to help them and babysit them to put quality system in place to do all I did say at the same time. We went into a clinic, we collected information to optimize in order to optimize this information. We actually hired a team in Indianapolis here, who worked for j&j on central IP and other companies, who knew how to take his information to better design and optimize the design of his devices. And when we had to try it in an in a in a non human primate to make sure that it will do what it's supposed to do. And when we got off technologies here in the country, in United States, we'll give our input, everything documented how it feeds how it will bla bla bla, and know it well, there. We are transferring the manufacturer here in United States in Minneapolis with Phillips and monitronics. Why just because again, of a capacity or capability, because somewhere, we need to make sure that this organization, they know how to manufacture, they have quality system, they have people to do it, they know how to do it, to document it, they can reduce the cost, and they can deal with supply chain issues, you know, today. So I hate to say to left France, for it was the right people at bedtime to be very hands on our design. But while we grow number two, our teenager, we need to go and go to a bigger manufacturer.
Patrick Kothe 26:14
So the product you've got designed freeze on the product the product is is completed, it's being manufactured your your partner is monitronics for make for making that particular component of the of the final product.
Patricia Zilliox 26:26
So I mean, it's when x is doing the budget and Righto Phillips, Rolex is doing the ocular device is is almost frozen. Yeah, we design is almost frozen. So you have to this is your feet of expenses, you have to develop the molding, you have to make sure you have all the tools and so we can go ahead with manufacture. I'm running.
Patrick Kothe 26:48
So Patricia, where do you stand with the device right now? Are you in clinical trials in humans? Where do things stand?
Patricia Zilliox 26:55
So that's an excellent question, too, because that's something that biological people don't understand. When you develop a biological uno or pharmaceutical, you do your thoughts, you go in human and you try if it works out in humans. In our situation, we had to get in between steps, which was can we actually do electro transfection in VI, does it hurt? Is it painful, and is the device perfectly designed? So we had to go into clinical trial, which we did in in injection in indication, which is called non infection, you're the IITs, it's a systemic disease. We're patient, I'm totally blind, there is no treatment available. And we'll go over that study was really to demonstrate that a we can put the device inject plasmid in VI, you can do electro transfection, it's visible by the doctor. It doesn't hurt the patient. It's safe, there's no burning or whatever. And we it's safe also for the plasmid. And also, we had to collect user feedback to optimize the device. We did it when alternating patient in France and United States in the UK. We did it, we got that done. We're down. So the challenge today is in front of investor and you ask the question, are we in clinical stage? Or are we not in clinical stage? We are not in clinical search of a target indication we have that we did very good technology in the clinical trial. Does it make sense? Say Yeah,
Patrick Kothe 28:25
it does. Yeah. So so you've got a portion of your, your clinical data, your proof of concept, so you're going to be moving forward with them. And we'll get to the fundraising side in a second because that's a fascinating, a fascinating thing. But before we get there, let's talk about regulatory, and what the regulatory strategy is for a combo product, US versus rest of world and kind of how you approached regulation and how you approached the development of the product based on what you heard back from agencies.
Patricia Zilliox 28:58
So when I joined the company with company was fine. So they dealt mainly with the French regulation. And a bit of a bad time the regulation on device was a little bit looser, this was a bit easy. I wanted really to move in the US because I wanted to work with the FDA. And I wanted to have accept acceptance of technology by ophthalmologists in the United States. I was here with Alcon best what I wanted, I knew that I could get that support here. So that's what we did. We did wonderful study in France. And when we did the study here, in terms of regulation, it's considered as about combo. So it's about logic. It's we are going to fall at the end of DLA, and it's going to be reviewed by the by the CBOE which is about the contribution of the FDA. In terms of devices. We have to obey and meet all the requirements from the FDA regarding devices. That's definitely like for a regular device, except we don't find for SEMA with them. For 510 K, for France in Europe, regulation has changed not very long ago last year, and no for devices, they basically aligned with the FDA. But as you know, Europe is not a happy family yet. Even if you have a new regulation in Europe, each country can still decide whether or not what type we're going to accept or not. So that's one of the reason why we're moving with clinical trial in the US only right now. Because as a small company like us, we don't have people and support in terms of man hours to go in each country and negotiate in each country, what type of regulation we're gonna want.
Patrick Kothe 30:40
So with a device, the device, just as it as it sits right now doesn't do anything unless it it's in combination with the biologic Correct.
Patricia Zilliox 30:54
Absolutely. Device along with long will do anything. So you have to integrate with biology with your device, which is this disposable, and when ocular device is linked to be electro transfection Punchinello.
Patrick Kothe 31:06
So from from a regulatory standpoint, is it a combination product? Or is the device regulated by one section, and the biologic regulated by another section?
Patricia Zilliox 31:20
So as I said, it's a BLS, it's about logic. And inside, you have two devices, and you have to make sure that these devices, every box have been checked for medical device, which is verification, testing, stability, blah, blah, blah, that's it. But I'd be any severe line which is being evaluated.
Patrick Kothe 31:39
Great. So let's, let's talk a little bit about where you where you sit, because doing clinical clinical trials is quite expensive to do that. Where do you sit on the funding side? And what kind of challenges do you have with funding when you're dealing with a combination product? Because in my experience, medical device, people do medical devices pharma, does pharma biologics does biologics? And these combos are a little bit tricky. So how have you found the capital markets for funding and medical or a combination product,
Patricia Zilliox 32:15
very difficult and very difficult, because I think you touched on it. Venture capital, they invest in a device, they know where the money is gonna go, and they know what's the cycle of his device, and they know when they're gonna get their money back, the venture capital will invest in biology, same thing, the cycle is longer that they know it. For us, it's duration is our enemy. Why? Because as I said a minute ago, we are in a clinical trial to demonstrate the safety of the device, now we have to go in clinical trial to demonstrate efficacy is separated. And that's a killer. Because for venture capital, it's too long. And it's too much money in too long. So but it has been very, very challenging. We have been able to secure some fun and still trying to raise $40 million while we speak. But the challenges, the people we're able to attract are people who really understand of technology very well. We understand the medical need and understand the value proposition while breaking. Because if you have venture capital in front of you just want to make money quickly. Very not gonna get it. We're not gonna like us, because we're too slow for them. Well, well, one other medical device well biologic and want to slow. They want quick, quick, quick, quick, as you know. So it has been very, very challenging to raise money for Cabo.
Patrick Kothe 33:39
Have you seen any difference being a French company, in terms of being able to raise funding the French
Patricia Zilliox 33:47
company, it is a challenge to because we're headquartered in France, but we're incorporated in the US. So technically, we're still a French company, the IP is in France, we could do what we call a flipper, which bring the headquarter here, but then you have to pay for the IP to transfer it, which we may do one day. But when you talk to venture capital, many of them they have an office in Europe, they have an office here we have an office in China. So if I talk to some of the venture capital here, we're gonna say, Well, you go to you go to the French office somewhere to to raise money, so we're not going to invest. So some of the venture capital don't like the fact that we're French. Absolutely.
Patrick Kothe 34:29
So if you look at look at kind of the challenges you've got, you've got a technical challenge. You've got a people challenge and IP challenge. funding challenge is funding the challenge that you're dealing with right now.
Patricia Zilliox 34:43
Yeah, I would say it's definitely the challenge. Because the device you know, okay, you get it. I understand. The biological okay, it's all about tox and preclinical. People, doctors, it's nothing different when I was doing a dalkom but the non is a challenge with doesn't mean it doesn't grow on trees. And it's definitely it's not data driven. That's what's difficult. You can go well you can pitch you can say you come from Alcon all the expense I have best team, it doesn't matter. It's not data driven. And that's as the challenge.
Patrick Kothe 35:19
Was this the biggest surprise that you've had in the past couple of years? I would
Patricia Zilliox 35:23
say yes, because I dunk on money was going on trees actually. I just didn't realize that. So I would say that's definitely the biggest surprise it hit me in the face very quickly. And I didn't expect it would be that difficult.
Patrick Kothe 35:39
So it really is interesting because it nothing changes, you still have a market need, you still have a product, you still have the all the challenges that we just discussed there. But it's getting people to understand the timelines and the risk associated with with the deal. Yet it's a little bit a little bit different pharma biologics, devices, they're they're all a little bit different. But it's it's a, it's a clinical challenge that you're trying to solve. And you've got a technology that can do that. It's really interesting to me that the funders are more hesitant on on a combo product.
Patricia Zilliox 36:20
What I'm really thinking 20 years from now, we're gonna see a lot of combo not only in VI, but everywhere. Diabetes, you mentioned diabetes today about insulin administration, I mean, it's going to be more and more common. I will not be surprised when one of these days we're gonna have these, you know, from the stem cells, or whatever we're producing, studying on Milan is going to be device combo about it, same thing. So in 20 years, we're going to be there. But in the meantime, we have to educate the field, we have to educate investor, we have to educate the regulatory agencies. Right now, I would say we are the one starting all these different thinking. But I will not be surprised in 20 years from now, it's going to be very common. I'm pretty thing so for every disease, yeah.
Patrick Kothe 37:07
Patricia, we haven't talked about reimbursement yet either for a combo combo product, does that change anything?
Patricia Zilliox 37:13
Yes, actually, it changed things in a positive way for doctors, because here you have a new procedures. So what you do, right, it's a new coding. And new coding needs better reimbursement for the person who administer procedures. And in terms of reimbursement, you still have to demonstrate the value of the therapy for your patients. So in our situation, we're going to be much cheaper than vital. Gene therapy, viruses have tremendous experience and expensive as we know, it's some of his disease for our periods. You know, we took about $500,000 a night or more. For us, it's gonna be much cheaper, easier to manufacture to, and new coding. So I think from a reimbursement I'm not panicking at all. Because I know that doctors gonna like when you coding, they don't make much money on IBT today. And for the patient and reimbursement agency, I know we're not worrying because it's going to be cheap Robinson God.
Patrick Kothe 38:16
So kind of kind of going back and you look at that there's a technical risk, there's a there's an IP. I'm like thinking from an investor. There's there's all these risks that come in here. And it sounds like the biggest risk that they're concerned with is timing. Yeah. Is that right? So is it because it's unsure? When you put A and B together? It doesn't necessarily equal C may equal zero Zed? Is it? Because that there's more when you put two unknown technologies that it could multiply the risk? Or is it just the overall timeframe is going to be greater than a device or a biologic? So I
Patricia Zilliox 38:55
feel you're well adding a risk with the device, definitely. And in terms of timelines, they like to see inflection point what what kind of inflection, I'm gonna have to reassure them and increase the valuation of a company. And that's what I'm lacking, you know, because everything is so slow with the device. I'm not I don't have enough data to reassure them on an ongoing basis. And therefore they don't they cannot predict when they're going to have a return on investment. And they need that. They want to be able to have a timeline on when we're going to get money back. And I can do it.
Patrick Kothe 39:31
So from an overall planning standpoint, if you assume that you have funding for this, what is the clinical trial length look like for the next trial that you're doing? Is it a two year with follow up? Or what does it look like?
Patricia Zilliox 39:48
So for AMD is very easy. It's very highly regulated by the FDA. It's slow disease progression. So these patients you have to follow them for two years for GA and you have to demonstrate these effects See, for what AMD is about one year, you have to demonstrate you have efficacy. Generally you have to enroll at least 200 300 patient minimum, that takes about one year to enroll. So you calculate one year and Holman, two years for follow up. And that brings your total to three years minimum, for what AMD? For years for drying, do you need two studies? And one study is generally about 60 $70 million. So you multiply by two. That's just for phase three.
Patrick Kothe 40:31
Yeah. And then once you once you compile all that data may take you take, you know, three, six months to compile that data get in front of the agency and review. And
Patricia Zilliox 40:41
it's a process, which is why I also added time, if we have good data in between the goal would be probably to get acquired by by a big pharma or go to IPO. And why is mature money is one of the overall
Patrick Kothe 40:56
well, that that is kind of the other funding sources in it. So you've got grant type thing, but that's not going to get you near the amount of money that you need. There's the VCs can do it. But there's also strategic investors. So for this particular disease state, is this our strategic investors, device companies? Are they pharma companies? Who is most most likely likely candidate?
Patricia Zilliox 41:23
So that's a good question, because in the United States, I would say this tweet, I thought initially would be a strategic investor would be somebody who does work on biologic and devices, they would be allergic for me, but actually, I think a small company was interested in BI and wanted to go in gene therapy with viruses and that got vehicle scared lately because of safety issue with viruses. But for me, they are very logical one, then the second question is Which farm I do want to go? In United States, you know, there's a lot of competition where we have a lot of us who would like to be acquired by Pharma. In Europe, you have less pharmaceutical company, you have all the the one in Switzerland, we're also here, so well, more American than Swiss. But then you have something which is called China, that would love your technology, because they have a very aging population, they are looking for assets, like oil, so that when you have a strategic decision, you know how to go over there? And what does it mean? So that's another question.
Patrick Kothe 42:31
Is this something from a go to market strategy is something that one company would sell the total system? Would you separate it out? Get your biologics here, get your get your device from separate company? Have you? Have you investigated that or thought through that yet?
Patricia Zilliox 42:49
Not yet. We, I mean, we talk about that, of course, and we have different opinion, all depend on the clinical trials. If, for example, if I'm just it's absolutely, you know, to, to hear it, for one indication, you have to inject every six months, and your indication you have to reject every year and repair image are not exactly the same, there's gonna be one aspect, if you can do the same device for any type of plasmid, it's a different approach. So we could do an approach where we license out some of the plasmid and we sell the devices disposable, and we do some coding so it cannot be used, or we pay by the fee by the user like you do for cataract surgery or for laser. We could do that. We have options. And I'm very honored to do we have not tackled this option yet. We have done this story a
Patrick Kothe 43:45
long time away from that. So so the devices is are the devices 100% of the device, disposable one time use product, or is there some some portion that is reusable,
Patricia Zilliox 44:02
the device is totally disposable. The pulse generator is going to be like an iPad, it's going to be in the office and we set it here. We'll just give it to each office for us. But we applaud devices disposable one time use.
Patrick Kothe 44:17
Well, it sounds like you've got your work cut out for you on the funding side to do it. But as I said, I mean, we're talking about a therapy and a real market need out there to have some technology developed here. Whether it's a device, whether it's a combo or a biologics really doesn't make any difference. It's the it's the therapy that's needed to solve this issue. Now it's a matter of how can you get through to the funders to make this happen?
Patricia Zilliox 44:49
Yeah, that's basically it.
Patrick Kothe 44:53
So Patricia, thanks so much for spending some time with us. Coming from far So, you've learned about device, you've learned some things about device. And you've learned that there's differences within the different tracks that we come from. What have you learned that you can apply that we can apply either if you're a pharma company, what can we learn about the device side? Or if your device what you can learn from the pharma side of things to make us better? Hmm,
Patricia Zilliox 45:26
that's a difficult question. I would say I focused mainly on pharma in when I was at Alcon is one thing on device, I would say, yes, you need the best engineer in the world to help you. But don't, don't go too late to see the user's real user. For me, I'll be ophthalmologist, and pick the right one. Not every of them on this board give you the best advice. Don't wait too late. I would say for us, we funder was enough technology. So that helps. But don't wait too late. Because that's also the one open except when you said market acceptance, we're gonna play a wall accepting new technology as well. And that's difficult to do. And the reason is difficult because we have a small team was 13 people. So we have to do everything. Dan, can we were just 20 people just to talk to a doctor about getting feedback on a device. But that's something that's a step which is critical. I don't think I did a fabulous job, I can be criticized about the job I have done. And I probably something I should do better, is getting the feedback from the user as early as possible.
Patrick Kothe 46:41
I think that's something that we all need to do. More of I've talked about this extensively on this podcast is getting customer feedback is one of the most important things that we can do before we even start designing a product is really understanding what their needs are. And having having clinicians involved in your development program is kind of a must. It but but it's not only just one clinician, it's a wide variety of clinicians, because everyone's got a piece of the puzzle. We all have a little bit of understanding of things. And sometimes clinicians can have differing viewpoints really need to design a product, given all of the feedback, not just who's on your medical advisory board. Yeah, and
Patricia Zilliox 47:25
for a small company. And what I want to say is, you know, if I if I have ophthalmology, listen to me today, because it Patricia, you need to walk the talk. Well, yeah, I know that. But you we are small team, and we have to do everything in a small team. And that's, I would say that's a challenge to you know, what you have to do I know what I have to do. And I don't do it all the time, because I don't have the resources to do it. So it's, it's, it's not easy.
Patrick Kothe 47:56
Oh, no, I totally get it the startup world is, is a different world. But at the same time, even if you're in a large company, you may have a lot of a lot of people there. But then you've got a whole lot of different priorities to you, you may be dealing with rolling out a new product or rolling out a new corporate program. So there's there's never seems to be enough time to do the most important thing. And it's talk to our customers. And I find that across startups as well as large companies, because a large companies in many ways that I've been part of them, you get you get large, you get arrogant, and you think you know, your customers, and the customers are always changing. So you really need to go out there, even as a large companies, you need to go out there and make sure that your understanding of what the product needs are actually the product needs.
Patricia Zilliox 48:44
And that's why icon was very good at when we talk about learning, I think that's something I want to touch on is to be close to the customer, but it's to be able to afford the time just for the customer.
Patrick Kothe 48:57
But Tricia is dealing with some interesting issues. Many of us have only dealt with medical devices. But imagine having to learn the basics and also the intricacies of pharma or biologics and then manage a development program. A few of my takeaways from today's conversation, first of all, the approach to learning as we said, you know, she's a company or the company is a biologics company that's developing a device. So what do you do? Do you go it alone and learn? Do you bring an experience to partner with experts? Well, she did a little bit of both. They started off going in alone and learning but then bringing in the experienced people inside the company and finally deciding to partner with experts. How this works for you. If you're managing a project is going to be different. Every situation is going to be a little bit different but taking a look at those options. Really makes sure that you're balancing off the dollars that you've got to invest the time to bring the product to market and then some strategic issues with dealing with partners and potential partnership opportunities as well as acquisition opportunities becomes really interesting to look at. The second takeaway was, what you think, you know, versus what real life is. Patricia kind of dealt with that when she thought that her experience and market opportunity were going to lead to easy funding really didn't turn out that way. Even though you've got great technologies. You've got challenges in developing those technologies and also challenges on the funding side because you're hitting something that's different than what other people expect. Finally, we started off with her experience with Alcon and I think it's worth worth talking about because Alcon is excellent company, and Alcon was dedicated to retaining good people. And the way they did that is through mentoring and providing opportunities to grow. As you're managing your companies just continue to focus on that. How do you retain people, it's focusing on them, and they're developed. Thank you for listening. Make sure you get episodes downloaded to your device automatically by liking or subscribing to the mastering medical device podcast wherever you get your podcasts. Also, please spread the word until a friend or two to listen to the mastering medical advice podcast as interviews like today's can help you become a more effective medical device leader. Work hard. Be kind
