Erectile Disfunction Treatment – On-Demand Erection with a Remote Control: Dr. Rodrigo Fraga, Comphya

Dr. Rodrigo Fraga, Comphya: 0:00

You know, Viagra works well, but for the 30% of the population it doesn't work. They need solutions.

Alex Jani, X-Health.show: 0:09

Hi, I'm Alex and welcome to the X-Health.show where I talk to visionaries behind the latest innovations in healthcare. For the eXtra health of the future. We're at EPFL in Lausanne, where throusands of tech savvy students enjoy their lunch in the sun, with a view towards the Alps across Lake Geneva. My guest today is Dr. Rodrigo Fraga, the CEO of Comphya. He has been researching vascular biology and male sexual functions for over a decade. With a focus on pharmacology first, he switched to medical devices. Comphya is as we startup on a mission to overcome erectile dysfunction in spinal cord injury and post-prostatectomy patients. Their CaverSTIM, a neurostimulator, can be implanted in the pelvic cavity to trigger penile erection with a remote control. You'll also hear about drug-resistant erectile dysfunction, recovery of damaged nerves after prostatectomy, and how does erection work in terms of neural pathways. [INTRO ENDS] When we first spoke, you just had the first implant being implanted in a patient. I wanted to, actually, asked about that implant but I came here today and you just said that the second patient had the implant inserted today. How was it? How did the operation go?

Dr. Rodrigo Fraga, Comphya: 1:31

Indeed, yes. Our team today is in Melbourne, they did the second implantation. And the implantation was wonderful, everything went smooth, which is great, because it is the first time somebody's implanted in human, and for long-term implantation. Of course, there's a lot of preparation for the safety of the patient, for the audit procedure that needs to take in place, but it went very well, very well, better than we expected, I would say.

Alex X-Health.show: 1:59

Okay, so we're speaking here, guys, an implant to restore erection. And we're speaking Melbourne. Who's actually the surgeon?

Dr. Rodrigo Fraga, Comphya: 2:11

One of the greatest things that Comphya managed to do is to partner with the best people in the world to do those trials. So we're doing this trial in Melbourne in prostatectomy patients. In Brazil we will start very soon in spinal cord injury patients. And as well in the US we should start quite soon. We managed to connect with the best neurologists in the world to do these tests. So we have Dr. Tony Costello and Dr. Phil Dundee – they're at the edge of prostatectomy surgery in robotic surgery. They are the best people in the world to conduct this work for us.

Alex Jani, X-Health.show: 2:52

We are now here in Lausanne and it's just after 10am, and the doctor actually is going into sleep now in Melbourne.

Dr. Rodrigo Fraga, Comphya: 3:03

Yes.

Alex Jani, X-Health.show: 3:04

You witnessed the first surgery, right, with with Dr. Dundee. How did that look like?

Dr. Rodrigo Fraga, Comphya: 3:10

The team there, they are specialists in robotic surgery. When the robotic surgery started about 20, 15 years ago, Dr. Tony Costello was one of the pioneers. So they know very well what they're doing. And actually it became a school in the in the robotic surgery. So it's a big center there. What we did, we came early, we did a lot of preparations, we did the trainings. They have an amazing setup for trainings. And as nobody did this before, it's the very first implantation, everything's new. We studied together with them in Melbourne, how do you implant it? How do you place the device? How do you suture? How do you bring the device in? And to our surprise, for the first implantation, everything went very smoothly. The device entered in via the trocar, because when you're doing a robotic surgery, have those trocars for the device to be inserted into the patient. So I would say it was a great preparation, a great teamwork – altogether, our team and the clinical team there that made everything very smooth. The system worked very well. Now we're waiting for the data, the results that are coming next.

Alex Jani, X-Health.show: 4:18

When do you expect them?

Dr. Rodrigo Fraga, Comphya: 4:21

In the coming months, so soon, we should start having the first preliminary data being released by the investigators.

Alex Jani, X-Health.show: 4:28

What was the patient's condition? Or, what can you tell us about the patient?

Dr. Rodrigo Fraga, Comphya: 4:32

Yeah, so we target different populations right there. There are different groups that when you talk about erectile dysfunction is not one type of patient. Erectile dysfunctions has multi-etiology. In Melbourne, we're targeting patients that are undergoing prostatectomy. Prostatectomy is the procedure when you remove the prostate to treat prostate cancer. When you do that, it is inevitable that you damage the nerves. So you have a mechanical damage of the nerves and then it causes erectile dysfunction.

Alex Jani, X-Health.show: 5:01

That's the nerves around the prostate?

Dr. Rodrigo Fraga, Comphya: 5:03

Exactly, yes. What is it actually, is a process in the brain that triggers the neuro system, as many other functions in the body.

Alex Jani, X-Health.show: 5:10

How does erection work in terms of the neural path that is involved? Because this is what we focus here on, right?

Dr. Rodrigo Fraga, Comphya: 5:18

Yes. The erection mechanisms, basic

Alex Jani, X-Health.show: 5:19

And now you focus on two of them.

mechanisms are like: 5:20

you have a process in the brain, the stimulation, that triggers the response. These nerves travel around the blood-spinal cord and then those nerves travel around the prostate, that's why when we remove the prostate, we damage the nerves, and then they go to the penis. When the nerves release neurotransmitters there, the main one is nitric oxide, when those compounds are released, they cause vasodilation. Vasodilation is when the vessels become bigger, you have bigger amount of blood into the organ. And then you have the engorgement. So this causes the mechanical reaction. If I sum up, it is a neuronal and vascular response. That's why when you have etiologies that relate to neurogenic pathways, it is damage in neuronal response, you may have erectile dysfunction, or if you have pathways that damage the vascular function, you also can have erectile dysfunction. That's why you have hypertension, smoking on the vascular side, diabetes. Or spinal cord injury – on the neuronal side, prostatectomy as well. Those are the two main causes for erection.

Dr. Rodrigo Fraga, Comphya: 6:32

We start, let's say, in the two of them. Prostatectomy – why they have erectal dysfunction? Because you remove the prostate, you have to because you need to treat the cancer – and this is a gold standard treatment for treating cancer. So you remove the cancer, but then you have this side effect – erectile dysfunction – which we are trying to recover. The other one is a spinal cord injury patients. And it's the same principle. You have a mechanical injury of the nerve, but in a in the nerve stimulation therapy, we stimulate the distal portion of the nerve to elicit the response. But also, we learned that there is a bigger population that we can target, what we call today "generic ED patients" – so patients that are stopping to use oral drugs, Viagra, Cialis, and the next therapies they have to use are quite problematic. So they have to use injections or penile prosthesis, which is very painful. There are many problems with this alternative.

Alex Jani, X-Health.show: 7:34

What are the problems?

Dr. Rodrigo Fraga, Comphya: 7:36

Injection– as you can imagine, every single time the patient wants to have a sexual intercourse, he needs to inject with a needle vasodilators into the penis. It's very painful, uncomfortable. Many people do it because they don't

Alex Jani, X-Health.show: 7:45

Doable, right? Because some people do it. have other solution. Today, there are many medications Painful. outside. The basic are, prostadine, papaverine – those are generic drugs, and then several formulations out there. But they have to use them, there is no other option. Pain, hematoma, and fibrosis over time are the main problems. And the

Dr. Rodrigo Fraga, Comphya: 8:03

Painful. And then he said, now I have second one is penile prosthesis. Penile prosthesis is a prosthesis you insert into the corpora cavernous. Corpora cavernous is the tissue of the penis, which looks like a sponge. So the doctor, to implant this device, needs to destroy the tissue, create the cavity inside the penis, and this prothesis stays there. So you have different models, the same same rigid inflatable devices that can cause a mechanical reaction. However, there are several complications. indication for penile prosthesis for pain of process, but I don't There is erosion, so then you need to do revision of the surgery. There is a lot of other problems related to that. Infection – there is a very high rate of infections. They now try to solve this problem but to compare to other implants, it's a very high level. And there are also many other complications. It is an irreversible procedure. So once you do that, as you destroy the tissue, you cannot revert it anymore. So that's quite complicated. And to give a picture of that, from the literature, of all elective patients for the implants today want to take the penile prosthesis. So for you, if your only 5% go for it, because it's really a problem. At Comphya we interact with many people recently and we interacted with a group in Canada called Praxis. It's a nonprofit organization, helping technologists to bring technology to spinal cord injury patients. So we interact with them, and we learn a lot. What was interesting, we met a few people, a few spinal cord injury patients with the same testimony. Saying, Look, I was using Viagra, now it stopped working and I started taking injections but ended up in the hospital a few times because of priapism. Priapism is when you have a very long erection... device comes to the market, it's great for me.

Alex Jani, X-Health.show: 10:09

Who are these people? Like, what are the characteristics of them? Spine injury – I can imagine it's mainly people who are active in sports or...

Dr. Rodrigo Fraga, Comphya: 10:20

Exactly, yes. So it's a specific population. Usually those come from injuries, accidents, you can imagine, motorcycle, paragliding, all the type of risk activities or accidents. And, of course, depends on the lesion of injury, then the patient can lose certain type of function. Of course, not all population will have erectile dysfunction. In some part they will respond to oral drugs. But the majority, they have erectile dysfunction, and they're looking for therapy. And what you ask, who are they – most of them are young patients. About 70% of the patients are between 15 to 35 years old, very young and highly active, their sexual life is highly active. So this is very important. And why we have a special care about this population is because they're looking for the solution. And I can cite one interesting article that was released in a major journal, this was about 10 years ago, they assessed 700 patients after six months after the injury. Okay, what's your priority of recovery? And for paraplegic patients, the first priority to recover is sexual function. Second priority is to walk again. Just highlight how important it is for them.

Alex Jani, X-Health.show: 11:44

I'm not surprised, really, because it was years ago, when I attended a sexologists congress and they actually were speaking about that, about surgeons who did their job, they did their job very well, and it's just, you know, there is this expectation that you should be happy, you are alive, right? What else do you want? And I'm very happy we are actually speaking about it now, because things changed, right? What I read while preparing for this conversation, I read that there are some surgical techniques now that try to not to damage these nerves – I'm speaking now about the prostate prostatectomy. So not to damage these nerves. So there is some awareness that this is important, right?

Dr. Rodrigo Fraga, Comphya: 12:33

Yes, there is. And you talk about prostatectomy, about the damage of the nerves. There is an important point, prostate cancer is a little bit different than the other cancers. It's not that aggressive, because sometimes, of course, it depends on the cancer, but sometimes the patient can wait a little bit. And what happens very often is the patient has indication for prostatectomy, to remove the prostate, but he's aware about the side effects. So what happens is he keeps monitoring and delaying the surgery. So Dr. Burnett, our clinical advisory board from Johns Hopkins, says this very clearly. What happens is, if you delay too much, you can make it worse. Sometimes the patient waits one, two, three years, keeps monitoring.

Alex Jani, X-Health.show: 13:17

Because it grows?

Dr. Rodrigo Fraga, Comphya: 13:18

It grows, it can get to the worst stage. Why he's doing this? Because he's afraid of the side effects. So our strategy, I mean, what we hope to do is to say, Look, now we have this device and the chance of infection is much reduced. So then the patient is not only treating erectile dysfunction, but then the patient will treat his cancer and as early his he's doing his prostatectomy, better is his recovery of cancer as well. So we treat not only prostatectomy, but we treat the prostate cancer better.

Alex Jani, X-Health.show: 13:48

How these two groups differ? So spinal cord injury patients and these prostatectomy patients?

Dr. Rodrigo Fraga, Comphya: 13:56

Good question. Actually, we see the product is the same, but we see two products, because this population is very different. For example, spinal cord, most of them are younger patients, and the main feedback is to recover erection, sexual activity. For prostatectomy, we also have the on demand aspect of the therapy, but there is an important aspect of the neurorehabilitation. Our early data shows that if you do low intensity stimulation, and that's the article we published with Dr. Burnett from Johns Hopkins, when we do that after prostatectomy in animals, of course, but now we show in humans, when you do that, you speed up the nerve regrow and the recovery.

Alex Jani, X-Health.show: 14:38

This was actually my question because I wanted to ask about that. I read about that, it makes sense, right? Because the nerves learn again, pick up the paths they left. How long it can last. Do you do you have any data about that?

Dr. Rodrigo Fraga, Comphya: 14:55

That's what we're going to see now. What we see in animals – it was very fast. In a few weeks there was a recovery of this connection. What we did is we mimicked prostatectomy injury and then we did this stimulation. When the animal is not treated with low intesity stimulation, there is nothing, there is no regrowth, there is no improvement. It's, like, flat. When you do the regrowth, in seven days, it almost comes back to the normal level. So the recovery is very fast.

Alex Jani, X-Health.show: 15:21

So you did this? No, Johns Hopkins did this...

Dr. Rodrigo Fraga, Comphya: 15:24

We did this in partnership with them. What happened is, it is not Comphya that figured out that when you do low intensity stimulation, you can regrow and reconnect peripheral nerves. That's known in the literature. Other people have shown that. What we show in this article with partnership with Johns Hopkins is we show in the same region. So in the prostate region, if we do the same, the same happens. We see that we can promote the same with our device. We place our device, the patient has his remote control. Mode 1 for on demand erection, for sexual intercourse, and mode 2 for low intensity stimulation to rehabilitate the nerves.

Alex Jani, X-Health.show: 16:05

Let's go back and start from the beginning, how does your device work? First, it's Comphya – let's start with that. What does Comphya mean, and why you named the company Comphya?

Dr. Rodrigo Fraga, Comphya: 16:19

Sure, yes, Comphya is from the Portuguese word comphya. So if you tell somebody comphya, it means you can trust. That's the message we want to bring to the

patient: 16:31

you can trust. And the principle of our technology is neurostimulation. So it was known for a long time that when you target the what we call, cavernosal nerves, so you apply electrodes on the top of cavernosal nerves to give electrical stimulation, you can elicit erection and maintain. And this was done 20 years ago. Now, as commonly happens in research, when you look to animals, and you translate to humans, there is a gap. If you look at mice, rats, dogs, even monkeys, when you open up, you see a single nerve, so you can grab this nerve, you see it, you put on top of it, and you produce erection. Now, if you go to humans, there is no cavernousal nerve there. You open up there is a plexus in this region, in the pelvic floor. So to simplify, you don't know where to place the electrode. And our technology is simple, we come with electrode array, we cover the whole area, we don't know which electrodes are touching the nerve, but we make sure we cover the whole area and at least one of the electrodes will be touching the nerve. So we implant the device when the patient is awake. What we're going to do is, we scan and see the best electrode touching the nerve. For patient A it can be 1, for patient B it can be 3 and 4. So it's going to change, there is a big variability between individuals. Then when he's awake, we scan and freeze those the best electrodes for each individual and then he can have the therapy. How it works, is like a pacemaker – electrodes in the pelvic floor connect to a pacemaker-like device. Those all are implanted, so the patient doesn't see it in the pelvic floor. Then he has a remote control. There's a remote control for the doctor to set up parameters, so you can see which electrodes to be used, which intensity he has to use for each patient,

Alex Jani, X-Health.show: 18:18

Does it happen in the operating theatre? Or before, or after?

Dr. Rodrigo Fraga, Comphya: 18:23

After. When the patient recovers after the surgery, we can scan, select the best parameters, freeze, and the patient has his remote control for the therapy.

Alex Jani, X-Health.show: 18:34

So going back to this first patient and the operating room. You said that was robotic-assisted laparoscopic surgery. So it's not, like, a huge opening that the doctor does, right?

Dr. Rodrigo Fraga, Comphya: 18:46

Yes, it's what everybody asking us. It is not that invasive, not at all. And we knew it and it was great to see in the OR, it's very easy to operate. So basically you have few holes in the belly, you place the device. And it's easy to access because the doctors... There is a big volume of prostate surgery and the way to approach the prostate and the pelvic floor, they know very well. So they can place the electrodes. For example, in spinal cord injury, so we did some assessment, they're going to have just four holes in the belly. We place the device inside and then the IPG, which is the stimulator, we place subcutaneous, in the small pocket. So it's minimally invasive surgery and the patient was back home the next day.

Alex Jani, X-Health.show: 19:36

I have the battery question. Where's the battery? How do you load it?

Dr. Rodrigo Fraga, Comphya: 19:42

The neurostimulator is old industry.

Alex Jani, X-Health.show: 19:43

How long does it last – recharging? It is there fo for 80 years, starting with the pacemaker. This is titanium type of can, like more pacemakers that are insulated – so everything's inside. And you asked about the battery. Our technology is at the edge of neurostimulation so that the device can be recharged by induction. So when the battery is down, the patient just needs to put a patch on top of it and by induction he recharges his stimulator.

Dr. Rodrigo Fraga, Comphya: 20:16

We're expecting that in three hours he can completely charge it, and he's going to do it every three months.

Alex Jani, X-Health.show: 20:22

So is it basically like charging a smartphone now, right?

Dr. Rodrigo Fraga, Comphya: 20:25

Exactly. But not every day, every three months.

Alex Jani, X-Health.show: 20:29

Every three months – that's a long-lasting battery.

Dr. Rodrigo Fraga, Comphya: 20:32

It's a good system, it is a very good system. We elect to have edge technology, so for example, so it is compatible with MRI. So the patient, who had the device implanted, can have the normal exam. Which is difficult for neurostimulation because it's a big titanic can and metallic piece. But this has been validated by us. And many other things. It is compatible with robotic surgery. It's important because in the US for example, 80% of prostatectomy surgeries are done by robotic surgery. So being compatible with this laparoscopic approach is important. And also for spinal cord injury patients doing it by laparoscopic... Because the healing process for spinal cord injury patients takes longer than the normal. And it's very important for them to be minimally invasive, so they have a better recovery.

Alex Jani, X-Health.show: 21:29

When actually can they have that operation done?

Dr. Rodrigo Fraga, Comphya: 21:32

For spinal cord it is elective surgery, so they can come anytime. And for example in Australia we recruited patients that come in for prostatectomy. In Brazil we're starting by the end of this month, we have some surgeries scheduled for the end of this month. So it's an elective surgery, we group them, they come and we do the implantation.

Alex Jani, X-Health.show: 22:01

Okay, and how, well, how do you know that the implantation works? Do you know this immediately in the operating room, when you were witnessing the surgery?

Dr. Rodrigo Fraga, Comphya: 22:14

We have some procedures. Of course, we do an intraoperative test. Before the implantation, we run a stimulation, we observe the erection, the moment of the surgery, and then the setup. So we set up parameters, and it's a clinical study, of course, we have the coming years, coming months, we have many endpoints and many checks, and then gold standard measurements for erection, satisfaction, and so on. That's what we're going to use,

Alex Jani, X-Health.show: 22:42

You said that the patient is awake, right? So can he say like, Yeah, okay, it works. Or how did that look like?

Dr. Rodrigo Fraga, Comphya: 22:52

So we used the standard, what the clinic and clinical researches do for erection. We measured erection, there's equipment to measure erection. Also the patient's satisfaction. So we have classic, validated forms that he fills up and gives his feedback. To sum up, we have direct measurements and indirect measurements that are gold standard for erection.

Alex Jani, X-Health.show: 23:16

Is that, like, 0 to 10 – How satisfied you are?

Dr. Rodrigo Fraga, Comphya: 23:19

Yes, yes.

Alex Jani, X-Health.show: 23:20

Okay. And the first patient, what was this 0 to 10 rate?

Dr. Rodrigo Fraga, Comphya: 23:26

We don't know yet, because we are collecting the data. We're waiting to see, but the expectations are quite, quite good. So far, I would say, that the investigators are very happy. So we'll see soon.

Alex Jani, X-Health.show: 23:40

That's a good sign

Dr. Rodrigo Fraga, Comphya: 23:41

Yes.

Alex Jani, X-Health.show: 23:43

How do you all do you train the surgeons? Or do they train themselves? Or what's your role, actually, in this operating theater?

Dr. Rodrigo Fraga, Comphya: 23:52

Well, it was teamwork because, as I say, they know how to do the surgery, we don't. We know the device. It was teamwork and we did a lot of preparations. We did cadaver study to understand how to place the electrodes. And we did phantom bodies, phantom surgery. It was great to be in Melbourne because they have a setup for surgery training. Doctors from all over the world come to Melbourne to train. It's a reference center for robotic surgery and they have a school. We took advantage of the school and we trained in the robots before going to the first patient, because we wanted to make sure, first of all, of the safety of the first patient, and make sure everything was properly prepared. We set everything up together with them and everything went very well for those two implantations, in terms of procedure, and also the patient recovery, there is no side effect, the system works very well.

Alex Jani, X-Health.show: 24:54

You were setting up the protocol from the beginning.

Dr. Rodrigo Fraga, Comphya: 24:58

Yes, we set that up together with the investigators. Yes, yes, because we have a sequenceL: now the implant and then in the next six months we follow up with the patient, checking. Of course, safety first and then the feedback, the effectiveness of the device, satisfaction, also the partner's. We have a part of this study to understand what does the partner feel about this.

Alex Jani, X-Health.show: 25:23

Random question: can the patient feel the implant inside?

Dr. Rodrigo Fraga, Comphya: 25:28

Now, he cannot feel it. It's internal so he cannot see it. Of course, if he touches the belly, he will feel the can of the stimulator, it is just under the skin. But he doesn't see it. He doesn't feel it. It's a neurostimulator, it's like a pacemaker.

Alex Jani, X-Health.show: 25:44

How did you get into this erectile dysfunction therapeutic area?

Dr. Rodrigo Fraga, Comphya: 25:49

To be frank, I don't know. I think it was how life gets in when it gets to the university. So I did

Alex Jani, X-Health.show: 25:52

Was it like a professor actually pharmacy school and my first research project in the pharmacy school was with erectile dysfunction. So that's how it started. working on it before?

Dr. Rodrigo Fraga, Comphya: 26:09

Exactly, yeah. We had a very good program called "Initiation to research". They take undergrad students for a scholarship to work 20 hours a week, and then you do research as a Master's student. And then you do your own research. And then I came to this lab, it was Professor Romulo, late, at the time, so he was doing erectile dysfunction studies in pharmacology. So I joined and then I started doing my studies there, and I did many studies in erectile dysfunction, again, in pharmacology. And then there were other researchers. There was one quite interesting, we were studying together with another professor called Elena. She was studying a venom of a spider that could be potential venom also to treat erectile dysfunction.

Alex Jani, X-Health.show: 26:10

Wow.

Dr. Rodrigo Fraga, Comphya: 26:10

Because they extracted from this venom some compounds that could be beneficial. And in this environment it started. That was my first research, it was interesting. I ended up doing my PhD. in another field, thrombosis. But then I began this erectile dysfunction in my postdoc, my first postdoc in the US – I also did some studying in the erectile dysfunction. I continued.

Alex Jani, X-Health.show: 27:22

[MID-ROLL] This episode is brought to you by the X-Health.show. And me. So if you like this podcast, be generous hit Follow, leave a review. That'll help me invite more such amazing guests for you. Thank you. [MID-ROLL ENDS] So when you started studying erectile dysfunction did you have any idea where do you want to end up with that? So how could the future of erectile dysfunction treatment look like? And then, how did that perception of this future change?

Dr. Rodrigo Fraga, Comphya: 27:57

Well, I think it was the evolution. You're looking at the problem and then you try to figure out a solution for the problem. We started with pharmacology, so we tried to find a drug, but I think the point is to keep the clinical problem in mind. Because at the end of the day, you don't want to do some research, you know, you need to have a proposal. The trigger is this: what you need to solve is the clinical problem. Pharmacology – it's a good way to go. We know we can find a good one, but we didn't really find. And then it came with the idea of using neurostimulation, which looks to be excellent. And we developed it and we now have good proofs. If your first question is how to come from pharma to medtech, I think it's not really the instrument but the problem. We want to solve a problem, a clinical problem. That's, I think, the gold point of coming for clinical solution.

Alex Jani, X-Health.show: 29:02

How did you convince Dr. Dundee to actually collaborate with you? I taking here Dr. Dundee as an example, actually, because you already mentioned that you collaborate with a center in Brazil and also Johns Hopkins. So what actually convinced them?

Dr. Rodrigo Fraga, Comphya: 29:20

I think first of all, they know very well the needs of the patients. I think they liked the technology and see the fit of the clinical need. I think that's the main point.

Alex Jani, X-Health.show: 29:34

What's that did you do before that, because you published some papers...

Dr. Rodrigo Fraga, Comphya: 29:39

Yes, we did publish because we did the interpretive study in 20 patients that we we showed the technology principle. So patients undergoing prostatectomy, we tested the device intraoperatively.

Alex Jani, X-Health.show: 29:51

What does it mean?

Dr. Rodrigo Fraga, Comphya: 29:52

It means that during the operation, the open prostatectomy, we had a window of 10 minutes to come with the device, place, stimulate and remove. So we were trying to understand if the array concept really works. And we did 20 cases and all of them responded, these were great results. So we published that. And that was the beginning, the start of proving the concept. Now kind of going back to your question, how we convinced the urologist, interestingly, we never had the difficulties to convince the urologist. All urologists we talk to, they liked very much the technology. I think, because they see the need, it's a big need, you know. They have thousands of patients going through prostatectomy and they know that the erectile dysfunction is a big problem. Viagra and Cialis doesn't work very well for those patients. And then they have this terrible solution: injection and prosthesis. It's a big, big problem in spinal cord injury and in other patients. I think they see the problem very well, because it's their life. And then they see the technology. And they saw the early concept that we did and there is a big potential. I think that's the connection. But it's good. We never had a problem convincing urologists. Actually, when we present them, they're always very excited to prove. And we're lucky to have Dr. Phil Dundee in Australia together with Dr. Tony Costello. In Brazil – Dr. Sidney Glina. In in the US – Dr. Burnett from Johns Hopkins. And also France, Francois Giuliano from Paris. We formed this, we called it, clinical advisory board, which is helping Comphya very much on the clinical research side.

Alex Jani, X-Health.show: 31:30

And they are also, I can expect, researchers themselves.

Dr. Rodrigo Fraga, Comphya: 31:34

Yes. They all are very highly experienced doctors. We are lucky. I mean, we kind of went as a sniper to find the greatest doctors around the world. And I think that's one of the main assets of Comphya. We really managed to get the best people in the world thanks to our technology. And for example, Dr. Burnett in US, he's, I would say, number one today in prostatectomy and sexual medicine. He was behind the discoverery of the mechanism of Viagra in the past. He did a lot of study on the nerve anatom, sparing techniques to avoid problems when you're doing prostatectomy. Tony Costello did the development of a lot of studies for robotic surgery – what's the best approach? Those are really the guys on the top of the of the clinical research in this area. So we are lucky.

Alex Jani, X-Health.show: 32:25

Lucky, lucky but how did you approach them? Practically – you, I don't know, met them at a congress or you sent them an email or you sent, like, hundreds of emails to the assistant, colleague one, colleague two, colleague three. How did that go?

Dr. Rodrigo Fraga, Comphya: 32:37

I'm a scientist, that's my background. So I was in the sexual medicine environment before. I knew Dr. Burnett and Dr. Sidney Glina from a conference. So we got to interact. And meanwhile we developed the technology and I talked to them in conference, and then they liked very much that. Tony Costello and Phil Dundee in Australia was a recommendation from Dr. Burnett. And things keep going. Francois Giuliano – we met in a conference, in papers, publications.

Alex Jani, X-Health.show: 33:08

Id does make sense, so you knew some of them from before and this actually started recommendations. Now, what did you do before – because you didn't work in medical devices before – your research was still in erectile dysfunctions but you were more on the pharmacological side? With what?

Dr. Rodrigo Fraga, Comphya: 33:28

Yes, exactly. I did pharmacology, I was studying vascular biology. Big part was erectile dysfunction. So I was fully on an academic path, when I came here to EPFL, I joined the lab of Professor Stergiopoulos and With electrodes, simple electrodes. we were working together initially on basic research. I saw, here at EPFL, a lot of development and Professor Stergiopoulos did found startups before that were of great success, and he developed the technology here. So it was Because that's how I used to do when I studied pharmacology, so you produce election to test any drugs. Then I saw the technology interesting, because I was doing nerve stimulation to evoke and one of the technology of Professor Stergiopoulos produce erection in rats. was a band, a gastric band that you can implant, and then you control it by a remote control, so you can expand outside the patient. While I was doing these experiments in rats, I said why don't we do this in humans? Implant and then you have an external control of what you're doing. This triggered the idea and we started working around it, the concept came, we did the patent and then we moved to the intraoperative tests and things evolved.

Alex Jani, X-Health.show: 34:48

How did you two meet?

Dr. Rodrigo Fraga, Comphya: 34:51

With Professor Stergiopoulos? Let me get back to 2011. He connected with my former PhD professor in Brazil and they had a collaboration together, a grant proposal between SNF and the Brazilian agency. At that the time I was in the US, my former professor contacted me and said, Look, you want to join the project?

Alex Jani, X-Health.show: 35:17

Because you already had this idea that these electrodes could work?

Dr. Rodrigo Fraga, Comphya: 35:20

I had the idea here. So I was studying, using those electrodes doing pharmacology. I was doing erectile dysfunction pharmacology here. And the idea came here. So we started the project together, I came here to Switzerland to be part of this project and we were studying atherosclerosis, muscular dysfunction, and erectile dysfunction as well. Then – merging. Because Professor Stergiopoulos is one of the greatest experts in the area of medical devices. So he founded successful companies in the past. For example, he's leading Rheon Medical, it is a drainage device to treat glaucoma. I think it was this merge of his expertise and I was coming here with erectile dysfunction expertise. We connected the dots and came with the idea of the electrode. And of course, we're not the only two founders. Mikael Sturny joined us, he did a PhD with us.

Alex Jani, X-Health.show: 36:27

What's his expertize that he brings?

Dr. Rodrigo Fraga, Comphya: 36:30

Mike– he's an engineer from EPFL, he developed his expertise here with his PhD. He's an expert in neurostimulation in erectile dysfunction.

Alex Jani, X-Health.show: 36:39

How did you actually pivot to medical devices from pharmacology? I mean, how and why. If we can go back to what did do research in before coming here to EPFL.

Dr. Rodrigo Fraga, Comphya: 36:57

I was testing drugs, understanding the biological mechanism. But at the end of the day, you're trying to solve a problem. So we were trying to get new drugs to treat erectile dysfunction.

Alex Jani, X-Health.show: 37:13

New in terms of, how would they be different from a viagra?

Dr. Rodrigo Fraga, Comphya: 37:17

You know, Viagra works well, but for 30% of the population it doesn't work. They need solutions. And as I said, they need to use injection or prothesis, which are today a terrible solution. We need to provide something better for them.

Alex Jani, X-Health.show: 37:31

So you worked, basically, on a better Viagra?

Dr. Rodrigo Fraga, Comphya: 37:35

Before? Yes, we were looking on it. But as I said, while doing the study, I was using the stimulation and said, Why don't we use neurostimulation?

Alex Jani, X-Health.show: 37:44

Alone?

Dr. Rodrigo Fraga, Comphya: 37:45

Alone, yes. Then I checked. Of course, people tried that before. Because you stimulate the nerve, you cause erection. And then we came with this concept of the array. Because what was blocking the technology to be developed was to find the nerve. With the array, we now believe we solved this problem. We need to be very specific in the pelvic region to target the nerve.

Alex Jani, X-Health.show: 38:07

I'm just thinking, why did you use these electrodes with pharmacological solutions?

Dr. Rodrigo Fraga, Comphya: 38:15

It was an instrument to start drugs. What we were doing this simulation in animals to produce a response and then use the drug to potentiate or inhibit the response. That's how you do pharmacology. So you administer the drug in the animal, you produce the erection and it is going to be smaller or bigger. That's the methodology. So not using the drugs – the methodology became a therapeutic method.

Alex Jani, X-Health.show: 38:56

I read that you hold seven patents. Could you tell a bit more about that?

Dr. Rodrigo Fraga, Comphya: 39:02

Yes. Mainly in the vascular side. I did patents for drugs for hypertension, pulmonary dysfunction, even alopecia. Also I have a patent for pharma for erectile dysfunction. And now, with Comphya, we did this first patent, the core patent and over time, as we developed the product, many other patents came. Today, with Comphya, we have about six to seven patents granted in the US, in Europe. Comphya has a very strong portfolio of patents today.

Alex Jani, X-Health.show: 39:50

And everything works on the erectile dysfunction or why so many?

Dr. Rodrigo Fraga, Comphya: 39:58

Because you need to protect many aspects. It's not only the method. We started with the core method, but then other things appear. So you protect the way you implant, for example. As I mentioned to you, nerve rehabilitation. It's one of the main aspects for prostatectomy patients because at some point you recover the function. Then there are other mechanisms behind that. So we came up with another patent. There is also an aspect of penile rehabilitation that avoids fibrosis to the penis, so then we patented this aspect. We try to protect as much as we can with the patents.

Alex Jani, X-Health.show: 40:44

Thinking now about the patient journey, there are several healthcare providers on the way. How are you going to ensure that patients will get CaverSTIM?

Dr. Rodrigo Fraga, Comphya: 40:54

That's a very good question. It depends where you are, in the country, and the health system. What we have assessed so far, some countries will be reimbursed by the system, some will not. For example, in the US today, neurostimulators are very well reimbursed. There are many codes, it's a very well accepted therapy. And penile implants are reimbursed. We see the scenario for CaverSTIM well accepted in the two ways. There are two arms for reimbursement in the US. Codes – there are existing codes that we can use. And other one is the patient benefits as they use penile implants. Of course, we need to bring clinical data, solid data, that will really benefit patients. By putting this together, this is very clear – we see they will be reimbursed there. In other countries, in Europe, it is the same. We expect that in the UK, German, France they're going to be reimbursed. But in some countries, it will not be reimbursed. For example, for some reason, in Switzerland, penile implants are not reimbursed. So here we see the scenario for reimbursement difficult. It will be privately paid in those countries. Also, we start clinical trial in Brazil, to understand the scenario there. Penile implants are not reimbursed there. But they have a big market, there is a big private implants market as well, even in those countries without reimbursement. So that's how we will operate. I mean, we, I think the easiest to get the reimbursement, so patients don't need to pay for it, or at least the patients will have a partial payment. So then it facilitates the patient to have the therapy. But also we see this private market scenario.

Alex Jani, X-Health.show: 42:46

What kind of costs are we speaking here about? What's the range? I mean, we're speaking actually two things, because the private cost will be different probably than the reimbursed one. But can you compare it to anything existing now?

Dr. Rodrigo Fraga, Comphya: 43:01

Yes, we're going to be in the range of penile implants today. So we can do that. Of course, we do have a premium device, we expect the comfort and the feedback, and effectiveness to be much better than what exists there. So we expect a premium device and in a similar price.

Alex Jani, X-Health.show: 43:20

Let me just ask you this marketing question, how big is the market really?

Dr. Rodrigo Fraga, Comphya: 43:25

That's, I think, one of the most attractive things of Comphya for the investors in the perspective. We have, let's say, three main markets. So it's spinal cord injury – it's a smaller market, very interesting, and there is a big need there. That's why we keep big attention. But the biggest market is prostatectomy patients and the generic patients. Those patients that are stopping reacting to Viagra and start the injections. We're talking about diabetes, smoking, hypertension. We're talking here about at least 3-billion market. Why? It is only the existing market. If you only take the smaller picture, what the penile implants are selling today, we're talking about half a billion. Just penile implants. There are today two big players, Boston Scientific, Coloplast – they sell together most of the implants in the world. And it's a big market for just one portion. I'm excluding here all the injections that come before that. So it's a really big market that we're addressing, quite an attractive one.

Alex Jani, X-Health.show: 44:28

I'm sure you've spoken with patients themselves, how do they see themselves in the operating theatre actually? Having the implant. Because it's something different than swallowing Viagra.

Dr. Rodrigo Fraga, Comphya: 44:42

It's different. Of course, it's implantation, but you do it once. It's minimally invasive surgery. But we're not comparing to Viagra. If the patient can take Viagra, it's easier. We're trying to substitute here injections and penile implants. These are terrible solutions. They are painful. They're problematic. And penile injections – the drop off is about 50%. In some scientific reports it goes up to 70%. Because of pain, side effects, you know, inflamation. Also it is not spontaneous. The patient wants to have sexual intercourse, he needs to prepare a needle, a swab. And it's a problem. We want to come up with a better solution. It's implantation, of course, but then the patient has a remote control for his therapy, it's much more comfortable.

Alex Jani, X-Health.show: 45:30

Do you forsee, at any point, he would have to remove it?

Dr. Rodrigo Fraga, Comphya: 45:33

Well, that's a good question also. Because for prostate cancer, we have this aspect of rehabilitation. And what we expect is that the natural function will recover. But there is no need, as we see, to remove it. So the patient can live with the device. It's for life. But for those patients we do expect them to recover the natural function. The rehabilitation of post-prostatectomy is one of our main target. So soon we're going to see, but it's an important aspect of the therapy.

Alex Jani, X-Health.show: 46:12

And with the spinal cord injury, that is no option for the rehabilitation.

Dr. Rodrigo Fraga, Comphya: 46:18

No because the problem is different. So the nerves are intact in the region where you simulate, the damage is upstream in the spine. So the aspect is really more the on-demand erection for sexual intercourse. We do expect other things to be improved, for example, which is very important for them, because as I mentioned, most of them are young patients, newly wedded or young couples. Ejaculation is a very important thing for fertility. And we expect to have improvement there. I hope that data will show that and that's why we put some expectations there. And also for the urinary function – we expect some improvement in the urinary function.

Alex Jani, X-Health.show: 47:04

Okay. And now back to the business side. What stage are you now at as a startup?

Dr. Rodrigo Fraga, Comphya: 47:11

We raised so far over 5 million.

Alex Jani, X-Health.show: 47:14

And you're looking for more, obviously, as startups do?

Dr. Rodrigo Fraga, Comphya: 47:17

Yes, we do. By the way, right now we have a bridge fund open. So our existing investors have joined. By the way, it's a podcast, if somebody's listening, is interested to join Comphya, is very welcome. So we're doing bridge financing. We want to assure the completion of this clinical trials, which by the way, is a very interesting point for investors to come. Because the clinical data that we're just getting now is a major inflection point in the value of the company. So we're doing right now this bridge finance, and then following the bridge finance, we call a Series A and then a big round for the pivotal clinical trial that we intend to run in the future. So we do have this bridge open, people that are interested to come, they're very welcome to connect.

Alex X-Health.show: 48:04

And the numbers you're looking forward to now?

Dr. Rodrigo Fraga, Comphya: 48:07

We're raising to finance the bridge – 1 million. With the existing vest, now we want to raise at least 500k more. So when you do the first implant, you need to be sure of the safety of the patient. There is long validation behind that. So that's why we spent a few years doing all the required validation, now we have the product there. So we start the clinical trials. What we foresee now, we're doing a pilot clinical trial, and also we're going to complete this about 20-30 patients. And then we want to do pivotal clinical trial, this pivot clinical trial is a big trial, we expect about 150 patients that we show in a bigger population, efficacy. And then we can take this data and come for market approval. After this pivotal we'll go for market approval. And then we launch the product.

Alex Jani, X-Health.show: 48:59

So market approval is a few years from now or how do you see this?

Dr. Rodrigo Fraga, Comphya: 49:05

It's about two and a half years from now. 2.5-3 years from now.

Alex Jani, X-Health.show: 49:09

And then the clearance, again, it needs a few years.

Dr. Rodrigo Fraga, Comphya: 49:14

It's a medical device, implantable device, it takes time for approval, because you need to raise this data, then you take these people to clinical trial. That takes time. And then you go into the regulatory process, the authoroties, requests – it takes time. But it's a big markets, it's the biggest need, so we're going in a good direction. We're doing an important thing. Even if it's longer away, it's a worth way to go.

Alex Jani, X-Health.show: 49:41

I can imagine that. So could you name the clinics that take part in these clinical trials now?

Dr. Rodrigo Fraga, Comphya: 49:49

In Melbourne it is Royal Melbourne Hospital, I'm very glad to have them on board, together with Australian Prostate Cancer, which is a reference center for treating prostate cancer. In Brazil, there is Mario Covas Hospital together, the medical hospital called ABC – it is one of the major hospitals in Brazil. In the US, we're doing the clinical trial at Johns Hopkins. And in France it will be the APHP system and Pitié-Salpêtrière Hospital. As I said, we're lucky to have the best clinics in the world and the best people to do the trials.

Alex Jani, X-Health.show: 50:31

And now speaking from the patient's perspective, when can patients actually expect to be able to have that device implanted?

Dr. Rodrigo Fraga, Comphya: 50:42

I think about one, two years and a half, three years from here, we will be in the market.

Alex Jani, X-Health.show: 50:50

Now, for closing, I'm thinking to link this operating theater we started with, the first implantation, how do you see the future of neuroprosthetics in general?

Dr. Rodrigo Fraga, Comphya: 51:06

Well, I think neuroprosthetics is the future. Today there are now many new technologies emerging in neuroprosthetics. But if you just step back, so if you see the body. What's the body? It's electricity, controlling function. So you have the brain, the brain gives impulse to neurons, and whatever you think it's neurons controlling functions. And then you go back, okay, you have pacemakers in the heart, Deep Brain Stimulation for Parkinson's, cochlear implants, and then you have sacral stimulation for urinary incontinence, and many other things are coming. There is an interesting one – you do a stimulation of an tibial nerve to treat urinary incontinence, overactive bladder. So the body is controlled by electricity. I think in the future, we're going to implant electrodes in different areas to solve specific problems. Because once you do the stimulation, you can activate the function or inhibit the function. And that's how we're going to treat diseases. The systems are there going to be improved – better electrodes, better stimulators. I think there is a big avenue for many technologies to emerge in the neuroprosthetics.

Alex Jani, X-Health.show: 52:17

All right, it sounds, definitely, exciting. So really, thank you very much for this conversation. And you guys, if you want to learn more about Comphya, please go to comphya.com. Thanks very much.

Dr. Rodrigo Fraga, Comphya: 52:36

Thank you, Alex.

Alex Jani, X-Health.show: 52:37

I'm totally impressed by the audacity of researchers turned startup founders. Doctors turned entrepreneurs or ordinary parents turned healthcare innovators. People battling the battles that no one fought before. For the eXtra health of the future. So if you see a startup posting on LinkedIn, show them some love, hit Like, comment, That's fabulous. If you have a couple drops more of that altruism, follow the X-Health.show, leave a review here. I'll be able to bring more of these visionaries to you. So a big thank you. You're awesome. See you next week.

SPEAKER: 53:10

The information in this podcast is for informational purposes only and should not be considered medical advice. If you have any medical questions, please consult your healthcare practitioner. The opinions on the show are Alex's or her guests. The podcast does not make any responsibility or warranties about guests' statements or credibility. While the podcast makes every effort to ensure that the information shared is accurate, please let us know if you have any comments, suggestions or corrections.