So, welcome everyone to today's webinar series. My name is Dr. Christina Lewicki-Gaup, and I'll be moderating today's webinar. It's titled Exonics and the Evolution in Sacral Neuromodulation. And we have the honor of having Dr. Karen Noblitt here to present. And the presentation should last about 45 minutes, if not a little bit longer, and then we'll leave some time for questions at the end. While most of you probably don't need an introduction to her, I will give you a quick bio. Dr. Noblitt serves as the Chief Medical Officer at Exonics. She's board certified in OB-GYN and FPMRS, and she recently completed her MBA at UC Irvine. She served on the American Board of OB-GYN Board of Directors, as well as the OGS Board of Directors, and she maintains her academic appointment at UC Irvine. She's published over 50 peer-reviewed journal articles and authored numerous books, and she is obviously a recognized expert in the field of sacral neuromodulation. So as you guys probably know, there's some housekeeping items. The webinar is recorded and live-streamed. Please use the Q&A feature in the Zoom webinar to ask any questions. We'll usually save those till the end. And if there's any tech issues, please use the chat feature, and OGS staff is monitoring to help with that. Thank you, Dr. Noblitt, and let's get started. Great. Thank you, Christina, and I wanna thank OGS for the opportunity for being able to present this. There is quite a bit of information we have that we'd like to get through, but I'll try to be mindful of the time as we're going on. And I wanna thank everyone who is attending live and look forward to your questions at the end. So as we go through, my disclosures, as Christine said, that I'm the chief medical officer at Exonix, and I have no additional disclosures. So when we think about neuromodulation, we obviously know it for sacral neuromodulation for the treatment of voiding dysfunction, for urgency incontinence, urge frequency, non-obstructive retention, as well as fecal incontinence. And that's where neuromodulation really plays a role in our day-to-day lives and for our patients. However, and again, that was approved back in 1997 when we first started being able to offer sacral neuromodulation to treat these voiding dysfunctions. But when we look to other sort of disease states and other industries, we see that there has been a technology renaissance as we go through. So back in 2005 is when we actually saw the first rechargeable current controlled system. And this was a device for spinal cord stimulation that was introduced by Boston Scientific. So you can see, even as long as over 15 years ago, we started seeing a rechargeable device come to market. And then it wasn't that long after, in 2008, where we actually saw the first MRI conditional pacemaker that was approved with Medtronic and their SureScan lead. So again, we've had this technology for almost 15 years to be able to provide MRI conditional devices to the market. We also, in that same year, saw the devices starting to become smaller. We saw the first miniaturized implant with a long half-life, or excuse me, long life, 10-year life. And then we started seeing full-body MRI compatibility in 2012. As we've seen sort of the evolution of this in other fields, the question comes to mind of, why don't we see this in our current field? So in 2000, we go back to 2015, and we start seeing a lot more rechargeable devices coming to market. We can see that if you look at the rechargeable versus primary cell, that we actually have more adoption of the rechargeable device, even as we see the industry growing. But historically, there have been some limitations with rechargeable systems. When you have to recharge a device, there is a charging coil that is housed within the encasement or the neurostimulator. And so in order to make it efficient and not too time-consuming, the charging coils have to be large. And the charging time may be much longer for these devices. Some of them had to be charged every single day. And because they were housed in an all-titanium system, there was the potential for that enclosure to heat up. And we did have one of the products that was brought to market have some trouble with heating of tissue, and it was eventually taken off the market. And when you have, again, a full titanium encasement or the can for the IPG, it can provide some limitations with regards to being able to communicate with external devices, such as a charging device or a patient remote control. So when we started looking at some of the historic problems, we were able to address many of those. And one of the things that was so refreshing to me as a physician, when I started working with Axonix back in 2014, as a physician consultant, is that when they approached me, they did not have actually a device already developed. What they had was the technology to be able to braze or put together a combination of titanium and ceramic. And the reason that this was important is that this ceramic portion of the IPG or the neurostimulator creates a translucent window. The titanium can, as I mentioned, titanium is really inefficient for the transmission of energy or to be able to communicate. And so that's why the charging coils had to be large. And then subsequently, the neurostimulators were much larger. And because of this inefficient transmission, again, that was a limitation for the other neurostimulators. But adding the ceramic portion to our neurostimulator, again, creates basically an open window where we have very efficient transfer of energy. So that allows us then to miniaturize our charging coil. And also a unique aspect of the ceramic is that it doesn't heat. And so we don't worry about the heating of that ceramic, even though we put in certainly safety measures and the ability to measure temperature, that ceramic portion does not heat up. So therefore we're able to actually create a very efficient process, a small charging coil and easy communication with the patient remote. So behind that ceramic window, in addition to the charging coil, we also have a radio frequency antenna that allows for the patient to have a remote control that they can have wireless communication at arm's length and be able to easily communicate with their neurostimulator. Now, if we think back into the past and we were thinking about overactive bladder, and we know that this is a chronic condition, this isn't something that you treat once and it's a one and done kind of thing. It's a chronic condition that needs a therapy that will be sustainable over time. And historically, we had Botox as an option to treat chronic overactive bladder or refractory overactive bladder. And we also had Medtronic InterStim 2 for sacral neuromodulation. But when we think about the horizon and take just sort of an average patient that we would see, again, this is a chronic condition, but we look at this horizon over say a period of 15 years, if the patient's getting Botox treatment, they would require, we think on average about an injection every six months or a treatment every six months. And if we look over that, that's 60 injections over that horizon. And historically with the Medtronic system, where the average device replacement was somewhere anywhere between every three to five years, they would be coming back to the OR frequently for device replacements. And we fast forward now to our device when it came to market. Again, we looked at some of the limitations and we did focus groups with patients to find out what they wanted from a neurosimulator. And one of the messages that was very clear is that they wanted to have something that was long lasting and they wouldn't have to go back to the operating room multiple times over the period of the treatment for this condition. And so they wanted something that again was long lasting. So when we developed our product, we went through very vigorous accelerated life testing to be able to qualify our device for at least 15 years in the body. And we say, qualified for at least 15 years, it's an open-ended qualification, meaning that when your patient gets to that 15 years, they don't have to actually have it explanted. And when we look at our accelerated life testing and the performance of our device over time, we expect it to last well beyond that 15 year horizon, but that's what we chose to qualify it for. And at that point in time, the longest approved device was for 10 years. And at this point we said at 15 years, we just sort of stopped that process and said 15 years is sort of our place where we think that's a good longevity for the device. The other, I think really wonderful thing about Axonix and the innovation that we provided and something that has been very refreshing to me is that when we brought to market our first neurostimulator and again, we did focus groups with physicians and patients to provide a neurostimulator that met the needs that overcome, overcame a lot of the barriers that we had historically with sacronar modulation. So when we had our first generation neurostimulator, again, we had MRI compatibility, we had the ceramic window that allowed us to miniaturize the device. And the charge interval was about an hour once every two weeks. Again, this was the largest charge interval that any device on the market had. But not long after that, we actually had our next generation, our second generation neurostimulator. So continuing to innovate, the engineers continue to improve the circuitry to improve the software and the hardware. So that now the charge interval was about an hour once a month to every two months. So again, that recharge interval was continuing to expand to make it much more convenient for the patient. We also heard feedback again from the physician community that they wanted to have more than one program, but probably two programs was that ideal sort of sweet spot. And so the third generation neurostimulator was then approved in March of 2021. So you can see in a very short horizon, we had continued to innovate to provide, again, consistent benefit for both the patients as well as the physician community. So now our device has the ability to, again, have a long charge interval, but also has two programs in it. And I can't really say much more about what we have in the pipeline right now, but rest assured, our engineers continue to improve the process and improve the efficiency of the device. And we'll have more to share with you next year. And hopefully on another webinar, I'll be presenting what's new with Axonix at that point. Now, one of the, I think, biggest barriers that many people had for offering sick renal modulation to a specific patient population or to any patients was the fact that we had limitations with regards to MRI. And so when we developed our product, it was done specifically with the thought process of wanting to have not only 1.5 full body MRI compatibility, but also to have compatibility for full body with 3T. And so our device was designed to minimize any interference in the MRI environment and have less MR susceptibility. So when we think about the testing that goes into this, we created over 8 million simulated sick renal modulation patient scans performed for both the 1.5 and the 3T to get the qualifications that we have. And we continue again to expand the MRI access so that when we first launched, we had 1.5 full body and 3T head coil MRI. Shortly after that, again, not even a year later, we developed our second generation and advanced this to our remote control that we were able to then look at the MRI readiness. The patient did not have to come back to the office, did not have to be visited by a representative to check the patient can simply use their remote control very easily to check the MRI readiness. And then in July, again, less than a year after approval, we had approval for full body MRI at 3T. And then shortly after that, we had approval for 1.5 and 3T upper and lower extremity transmit and receive coil scans. So we continue to, again, expand the MRI access so that currently with the approvals that we have, we actually have the most liberal conditions around MRI access. And we can cover at least 95% of the MRI scans that your patients may have with our current approval. And we are, again, the only company at this point that has approval for upper extremity coils. So when we think about the, you know, we look back historically when we saw back in 2008 where the first implantable device was approved for MRI compatibility or MRI conditionally approved. And now we see that with sacronary modulation, we are at the leading edge of MRI access. So instead of sort of being behind and being more of a laggard, we're now really the leader in access for sacronary modulation and MRI. And this is compared to a fully implanted spinal cord stimulator or deep brain stimulator. And we're at the leading edge of MRI access with 3T MRI where the sacronary modulation really now is the only system, implantable neuromodulation system that has full body 3T MRI access. When you look at the spinal cord stimulators, deep brain stimulators, these systems do not have full body 3T MRI access approval. So now in a very short period of time, you know, we have become now the leader in access for MRI. Now, one of the things that I mentioned earlier was when I started working with Axonix back in 2014 and I met the leadership team, they met with me, but they didn't have a device or they didn't have the patient facing accoutrements already developed. And that was really refreshing to me is that Axonix really is a very customer centric company. And when I say customer centric, I mean the customer, meaning the patient as well as the physicians. So before they went out and designed any of the system, they actually ran focus group with patients. So they brought patients in who were using spinal cord simulators and having to recharge. They brought in patients who were using sacro neuromodulation and using the remote. And they asked them, you know, what are your challenges? What do you like? What do you not like? You know, what would you like to see out of your ideal system? They did that also with the physician community and said, you know, what do you like about neuromodulation? What are the limitations? You know, what are your pain points? What would you like to see improved? And that's what informed the development of the product and the product that we have to offer today. So we wanted to make sure that we could provide the best patient experience and the best clinician experience. So if we start in just thinking about, you know, one of the challenges that we've had in the past was around programming and the patient's ability to change their own programming. And so we wanted to do was to really simplify the process. We wanted to reduce the patient fuss and we wanted to really enhance the therapeutic outcomes. And the way that we did this was we developed an intuitive clinician programmer. So it's very simple to use. It's a bespoke product developed fully at Axonix. It has a color touchscreen tablet that allows us to program and provide case support during the lead placement and then programming the patient postoperatively or programming the patients in the office. So what we built into this clinician programmer was a proprietary algorithm. And so what the proprietary algorithm does is it takes your specific patient's intraoperative responses and provides you the four best programs or suggest the four best programs to start with based on your patient's response. So instead of taking seven or 11 standard programs and, you know, trying to toggle through those or having your patient go home and figure out which one works the best, our proprietary algorithm, again, takes your patient's specific information that was generated intraoperatively and will suggest the four best programs to start with. And we are currently running a registry study where we're actually looking at the efficacy of this proprietary algorithm. Now, something that you may have heard about because we've been talking about it a little bit more, but something that I certainly was not aware of when I was thinking about providing sacronal modulation was how we were delivering the energy. So one of the things that I learned as I joined the company and started working with the company was about constant current stimulation. And constant current stimulation is just one way to provide energy. The other is a voltage controlled system. So I don't want to give anybody post-traumatic stress about thinking about physics and going back to Ohm's law, but this is all based on Ohm's law. So we all know as surgeons, anytime that we do surgery, we implant a foreign object in the body, it's going to create scar tissue around it. And so you can see the lead placed along the sacral nerve root, and over a period of time, as the lead scars in, it builds up that scar tissue around it, and that then increases the impedance. So now we have, again, a barrier for that energy that's being transmitted from that lead wire to actually get to the nerve. So we see from studies, and this was a study that I was involved with, the insight trial, when we looked at an increase in impedance over time, you can see that, again, it starts to increase about that four week period of time, we start seeing that scarification, and that increases out to, again, about six months, where it sort of stabilizes and levels off. We also reproduce those same results in our two clinical trials, which was the artisan and the relaxed trial. So whenever you implant a lead, we do see consistently that the impedance increases over time, and that's just due to that scar tissue buildup. So when we think about a constant current system, that means that when you are setting the patient, the patient is set at a certain current, and that current will stay the same. And current is what activates the nerve and allows the patient to receive the therapy. So if you set the patient at a constant current, and if we think of, again, Ohm's law, where the voltage equals the resistance times the current, in a current-controlled system, if we set the current then, as the impedance goes up, our device will automatically increase the voltage to keep the current the same. So the patient does not have to then bring out their remote control. They don't have to increase the stimulation to maintain the same current. It will automatically happen. We look at a constant voltage system. Again, if we set the patient at a constant voltage, then we have the resistance times the current. So as the impedance goes up, if the voltage is kept current, as the impedance goes up, which we know it does, then that means automatically the current will have to go down. That's just based in physics. And so what you're seeing here on the left side of the screen in the green, in a constant current situation, even though you have an increase in scar tissue and an increase in impedance, in a constant current system, the voltage will automatically increase to keep the current the same. In a voltage-controlled system, which is like the InterStim 2, when the voltage is set, as that scar tissue goes up, you can see that the impedance will go up, the current goes down. So you see that sphere that decreases, it's demonstrating the decreased current that's actually being delivered to the nerve root. And so what the patients have to do in that situation is they have to actually bring out their remote control and increase the voltage to keep the current the same. So the way that it's a pretty easy analogy, and this is something that I found easy then to explain to patients as well, it's like a cruise control. So a constant current system is like having cruise control in your car. So as you set the speed and you get to a hill, that's that impedance, in a cruise control situation, the RPMs automatically go up to keep you at the same speed. And you don't have to do anything. You don't have to step on the gas or do anything manually in a cruise control system that will automatically increase the RPMs to keep your speed the same. And that's what a constant current system is like. In a voltage control, it's like having a car without having cruise control. So as you hit that hill and you start going up, you have to actually manually do something. You have to step on the gas pedal to maintain that speed. So you have to manually do that. And that's a voltage control system. So again, it's just taking another pebble out of the shoe for the patients as, again, they're going through the healing process of having to adjust their stimulation to keep them in that therapeutic zone. And this is a study that we did just demonstrating with our system from, this is from our artisan trial, looking out post activation out to six months. The green line represents the current in milliamps. And you can see there's very little change. So because our system is a constant current system, the patients really didn't have to do anything. And their current stayed really consistent throughout that time period out to six months. Had it been a voltage controlled system, you can see that black dotted line. The patients would have had to increase their stimulation to keep the current the same. So this is what we're seeing here, that black dotted line is over time, the voltage automatically increasing in the constant current system to maintain that current. So the patients, again, are staying in that therapeutic zone more consistently because the current activation is staying the same, again, over that horizon. So lastly, in talking about the sort of the evolution and the innovation that we brought to bear, and this is probably my favorite part of the whole system, is the patient remote control. And one of the things that we heard loud and clear from the focus groups of the patients is they wanted something that was really simple to use, it was easy, it was convenient, and it wasn't stigmatizing in any way. It didn't look like a medical device. It didn't look like if they brought it out that they were having a medical device in their hands. And you can see the form factor is very familiar. It looks just like a key fob. And we had one of our physicians share a story with us recently that one of her patients who had an implanted Axonix device, her husband was looking for the key to their car, went through her purse and actually pulled out her remote control and was trying to open the car and couldn't understand why it wouldn't unlock it. So we think, you know, we hear stories like that, that it really is functioning exactly as we intended it to. So you can see here holding it in your hand, it's very small, simple to use. We only have three different buttons. You can see at the top there's LED light. So what we wanted to do was take out any engineering language that the patient, you know, would be seeing. So we don't talk to them in terms of frequency and pulse width. They simply have a level that they know they're at. And so you can see at the top, those LED lights, there's seven different lights. And each patient will go home on three different lights. So it also allows us to really troubleshoot with the patients. If they're calling back and saying, you know, it doesn't seem to be working or I'm not feeling the stimulation, we can simply ask them, how many lights do you have on? Oh, I only have one light. Okay. Well, simply take the up arrow, go up until you can feel the stimulation. So we can actually troubleshoot that versus if the patient called in and said, you know, I'm really, you know, I'm, you know, not, it's not working. You know, what is your level? I am at, you know, 2.2. Well, we don't have any relative information to know where that patient started. Is that higher? Is that lower? But knowing that each patient goes home on just three lights allows us to sort of troubleshoot. The up arrow, they increase the stimulation. They will actually see another light appear, but they also have a little vibration that will confirm that they have, you know, increased the stimulation. There's a down arrow that allows them to go down. The middle button allows them to communicate with that. And there's a simple process for confirming MRI readiness, as I mentioned before. And one of my favorite things about this is there's no battery replacement. This device or this patient remote does not have to be charged. And there's no batteries in the back of it. So you don't have to be, you know, a battery store and have, you know, the AA or AAA batteries that we used to have to carry in our office because patients would come in with their remote. They hadn't either taken it out of the box or they hadn't changed the batteries and they were dead. So again, we wanted to simplify the process. And this is the patient remote that we are currently using today. So you can see the patients can hold it at arm's length. There's no communicator. They don't have to hold anything, you know, over their neurostimulator to communicate with it. They simply hold it at arm's length and they can communicate very efficiently with their device. Again, coming back to that ceramic window with that radio frequency antenna behind it allows for very efficient communication. This is just showing, again, a little simple close-up picture showing the stimulation level, which program they're at. They connect to the stimulation, you know, to their neurostimulator with the middle button. They can simply turn the stimulation up or down. And at the bottom, there's an indicator light. That indicator light will tell them, you know, where they're at with the charge of their neurostimulator. So if it's green, that means they have more than four, you know, four days or more. So they're good to go. When that light turns an amber color, they have somewhere between two to four days left of the battery life. And when it starts flashing amber, they have two days or less, and it sort of indicates to them they probably should charge. But I would say most patients start habituating around when they charge and may not actually even use this to decide when they're going to charge or not. So I'm going to play this video just to demonstrate what the patient's experience is with the remote control. And this is really personal to me because the patient that's in this video was actually a patient of mine that I had implanted with an interstem many years ago and probably didn't do that great of an implant because I then had to replace her IPG at four years. And then her lead wire fractured, the impedances were off, and she was going to have to come back for another replacement. And at that point, I had just joined Axonix, and she called me and learned about our device. And she had both fecal incontinence and urgency incontinence, and then learned that she could have a device which was MRI compatible, had a 15-year life. She decided to wait until we had actually FDA approval, and she was our first commercial implant. And so she's had the opportunity to compare both her experience with the interstem and our device with the Axonix device. And again, because of the limitations that she encountered in her own personal life, she had been recommended to have an MRI in her early 50s in the period of less than 10 years was going to have a third surgery. That's what led her to make the decision to wait a little bit over a year dealing with fecal incontinence and dealing with urgency incontinence to have our device. So this is Melissa's story. The Axonix remote is wonderful. It's so easy and simple to use, and it's very light. I keep mine in my handbag. That way it's always with me, but I must say I hardly ever have to touch it. I don't think they could have made it any simpler. The interesting thing is you only need to hold it just right by your body. You don't have to put it anywhere, attach it anywhere. It's a wireless remote, so it's absolutely amazing. I never have to worry about putting batteries in it. It just works, and that's the best part. The E's don't have to think about it. It's fabulous. So that was really, again, one of the things that we wanted to make sure that we focused on was not letting the patients defeat their own therapy by having a remote, a patient remote that was confusing. So we wanted to make it really simple and easy to use, and we've heard great feedback not only from patients in our clinical trial, but also after our commercial launch. Now, of course, the other important aspect of our system when we brought this to market was we were the first rechargeable system, and as you can see in the other implantable devices, the rechargeable really became sort of the market leader over a primary cell. So this is where we're seeing a lot of the new technology that we're And so this is where we're seeing a lot of adoption of a rechargeable device. And so we wanted to also then make sure that the charging experience was going to be a very consistent, reproducible, easy process for the patients to do. So we, again, designed our product with all of those things in mind. So with our device, we actually, as I mentioned earlier, with our our second generation neurostimulator, we increase the charge interval from once every two weeks to, you know, about an hour once every month, excuse me, once a month to once every two months. And that depends on, again, the settings. But the nice thing with our device is that the patients can choose, they can customize their charging experience. So if you have a patient that likes to top off every day, you know, they just want to, you know, I'm brushing my teeth as I get to bed, I'm just going to pop my my charging belt on and charge for a few minutes. Or I want to do it once a week. You know, I watch a certain TV show. I'm going to charge maybe for, you know, 10 to 15 minutes once a week. Or I want to do it once a month or even less often than that. They can actually customize it to where it's convenient for them, where it fits their lifestyle. And there's no decrement in the performance of the battery or the battery life. We again wanted to make it very simple to use. We have this little belt. The charging puck just snaps into it. The patient places it over their neurostimulator. They get a tone that signifies they've connected. And then they can go about their activity. We wanted this to be a very easy process. We didn't want them to feel like they had to sit down. They don't have to be plugged into anything. They can walk around and do whatever activity. And then they'll get some rising happy tones when they are completed with the charging. And one of the things that we were able to learn from our other industry partners that had rechargeable devices, and again, some of those devices they had to charge them every day and they were charging for, you know, hours at a time, was if the patients thought they were charging and their charging puck moved a little bit away from their neurostimulator, the patient may not have been aware of that. And so what we did was we put in a system where if the charging puck moves a little bit away from the neurostimulator, it makes sort of a barking noise. But not only that, it also then will vibrate. So if the patient has any hearing impairment, they will still be made aware that they need to just adjust their charging puck back over so we make sure that they have an efficient charging experience. And this was something, again, new for us. And we wanted to be able to evaluate how patients were doing with sacronaural modulation and recharging. And so this was a specific endpoint in our clinical trial and our artisan trial. And we found that 94% of the patients felt that charging, their frequency, the duration, the whole process of it was acceptable. 94%. So again, that is a huge number and something that was very encouraging to us to know that we were able to provide patients with a really reproducible and efficient process for their charging. And one of the things, you know, many of our study investigators in the beginning had a little bit of hesitancy and were somewhat skeptical. And we weren't used to having a rechargeable device on the market. And some of the study investigators were saying, oh, well, my older patients may not be able to use it. Maybe we shouldn't implant in that patient. But again, we didn't see any difference. And you can see this is one of our patients, Donna, who really has no issue with charging, no issue with the remote control. And that's what we found consistently, regardless of our patient's age. Now, one of the things that is really important is obviously to see how this battery performs over time. And we actually will go through a process. We talk about that accelerated life testing, going through the process of charging and completely discharging over the cycle to reproduce that 15-year horizon. And you can see with that process, at the end of that 15-year horizon, we still have 99% of the battery capacity. And also, when we see this in in the INS performance, when it's at body temperature, we also see no decrement in the device performance. So what that means for your patient is that when they have it implanted, at that six-month period of time, if it's taking them 20 minutes to charge once a month, 30 minutes to charge once a month, at 10 years, they'll still have that same charge experience. So it's not going to take them any longer. It's not going to be more frequently with the charge interval. And we actually have clinical data that shows that performance of the device is consistent over time. We also have software and hardware built into our system that protects it against a full discharge. So even if the patient lets it go into hibernation, or say a patient becomes pregnant, the recommendation is to turn the device off, the patient can simply charge that back up easily after the delivery. And it will not fully discharge, and it will not cause any decrement of the battery capacity. Now, there has been some recent information that's been circulating out there indicating that our device does not function as well if it's fully discharged. And that's really true of a lithium-ion battery. Now, we chose a lithium-ion battery because it's a great battery. It provides a lot of battery capacity, which is why we have such a long interval. But in that system, we built in protection against that full discharge. So with the software and the hardware, our device cannot be fully discharged because of that. And so we have not only the longer battery or the higher battery capacity and the longer charge interval, we have protection against that fully discharge. So we can confidently say that our battery functions will be consistent, and we have no decrement of that battery capacity over time. Again, you can see at that 15-year horizon, we still have 99% of that capacity. Now, this is, again, one of our patients from our initial trial, Wendy, who is celebrating her five years. So she is one of our first patients that came back for her five-year visit from our RELAX-OAB trial. And she has had no change in her charging experience. She can go as long with the interval. It's not taking her any more time to charge, and she's very satisfied with that. So again, she's celebrating her five years. She says that if anybody was thinking about them, she would tell them to do that, that she has no trouble charging. And instead of, again, at this five years, where if she'd had a non-rechargeable, would be going back into the hospital for replacement and recovering from her surgery, she was out instead celebrating with her family her five-year anniversary. So again, we wanted to optimize the patient's charging experience so that it would be consistent over time, that it was comfortable and would be, again, sustainable. And so we continue to innovate and improve the process. And one of the things we did learn from our early commercial launch as well as from our clinical trial was, as we all know, not everybody's body habitus is created equally. And so we improved upon the charging belt. So it was really more form-fitting. We actually did focus groups with patients, and the feedback from this has been really very positive with regards to patients having improved usability with the belt. Also, patients, you know, can actually have an automated reminder to charge. So if they don't want to think about it, they haven't habituated around it, they can actually, if they opt in, get a text or get an email that says, okay, remember, you know, you're at, you know, six weeks, you're at, you know, one month time to recharge. So they don't have to actually, you know, think about that if they don't, you know, want to set a reminder, haven't, you know, set up a system for them, we can help them do that. And then also, we have one of the things that's been really important to me, and something that I hadn't, you know, thought of, and I wish that I had this, you know, when I was in practice, was that we have hired a group of specialists. So they are therapy support specialists. And their only job is to actually reach out and call patients after implant, because we want to make sure that every patient is doing well. In fact, our mantra is, you know, no patient left behind. And so these therapy specialists are actually calling patients, you know, at three months, six months, nine months, one year, and then yearly after just checking in to make sure that they're doing well. And that's their only job. And we're able to troubleshoot the majority of any patients are having questions or having issues. And, you know, from our standpoint, from medical affairs, from product management, we also get involved to help troubleshoot these issues. So that really helps make sure that your patients are continuing to do well. Because we all know, again, if we don't see patients back in the office, we make the assumptions that the patients are doing well, and I'm just as bad as any other physician. So we want to make sure that those patients aren't walking around out there and not getting the therapy that they should be getting. So this is something from a physician standpoint, and a customer support standpoint that I think is very, very important. So again, these are the things that we've done to help optimize the charging experience. Again, the charge interval, we have a smart charge tool that also helps optimize the charging experience by having patient-specific charging education, and then that curb belt, as I mentioned, which is a little bit more form-fitting for the majority of patients. So again, the feedback on the attributes of the Axonic system was, again, the things that are important to them were this long life, having a device that was MRI conditionally safe with really no barriers to being able to have access to an MRI scan, and then an easy-to-use patient remote control. And so I know I have just a few minutes here left, and I want to check in with Christina to make sure we have time just to go through quickly some of the clinical data. Absolutely, Karen, go ahead. Okay, perfect. So some of you may have already been aware of the two studies that we ran. And this, again, from a physician standpoint, this was really important to me, not only to have that innovation portion of this in a therapy that it was long overdue to have this innovation, to be able to make it more accessible to patients and more patient-friendly and more physician-friendly as well. So we had all that innovation, but it's also important for me as your colleague and peer to be able to have clinical data to share with you, to talk about our device, and to, again, stand up in front of you and recommend the use of our therapy, because it's backed by good clinical data. And so we ran two clinical trials. I'm going to just really focus on the Artisan Saccharin Remodulation Trial. It was indicated for urgency and continence. We had 19 different sites, 14 in the U.S. and five in Western Europe. And based on the number that we needed with our power analysis for the FDA, we only needed 116 subjects. We actually enrolled 129, and we did this in record time, in just over six months. And the reason we had 129 was that there was a huge acceleration in the enrollment in subjects as the physicians started doing their first implants. They were very excited about the therapy, and so we didn't want to exclude any patients that had been enrolled, and that's why we ended at 129. So the inclusion criteria, the patients had to have at least four urgency and continence episodes on a three-day diary, had to have primarily, you know, if they had mixed incontinence, it had to be urge-predominant, and they had to have a chronic condition. So they had to have history of this for over six months, and it failed other conservative therapies. We, you know, this is just a small list of the exclusion criteria, and they were really pretty much the usual suspects of a inclusion-exclusion criteria. So if they had mixed incontinence that was stress-predominant, if they had any evidence of mechanical urinary tract obstruction, any underlying neurologic condition, if they had uncontrolled diabetes as diagnosed with a hemoglobin A1c of greater than 8, they were excluded from the trial. What was interesting also about this trial is that it was done in a single non-stage procedure, so we didn't have an external trial period to see, you know, will it work or not, or are you going to get the the neurostimulator? All patients had a full implant at the time of surgery. We did have intraoperative screening criteria, so the patients had to have at least two electrodes at four milliamps or less to get the implant. We had no intraoperative screen failure, so of all the 129 patients that underwent the procedure, all 129 were implanted with the axonic system. So then the patients were then evaluated at that one-month period to see whether they were a therapy responder or not. So again, this was a unique design, and this was informed by our physician advisory board in that we knew sacroineuromodulation was an effective therapy, and we were looking at really the device performance and the safety with our device, and so the feedback from the physician advisory board was, let's just do a single-stage implant and save the patient, you know, two trips to the operating room and just have one surgical procedure. It also gave us a unique opportunity to look at those patients who were considered sort of non-responders based on the voiding diary. So our assessments for efficacy was on that three-day diary. We also wanted to look at the patient-reported outcomes, so we used the ICIQ OAB quality of life questionnaire. We also wanted to collect data on fecal incontinence, even though it wasn't a primary aim of the study, so we had the patients fill out the Cleveland Clinic fecal incontinence score at baseline, and if they scored six or greater at baseline, then they also then reported on that at follow-up. We collected, you know, all the safety information. We were governed by an independent review with a data safety monitoring board, and then we looked at device performance. Now, when we looked at the data analysis, because we just had a full implant, patients were considered to be either a therapy non-responder or a responder at one month, and they had to have a greater than or equal to 50% reduction in urgency incontinence episodes, so the usual definition of success. And again, at that one month, if they had a greater than or equal to 50% reduction, they were considered a therapy responder. If they did not have that 50% reduction based on the diary, they were considered a therapy non-responder. However, we continued to evaluate all patients throughout the entire two-year period, so again, in the insight trial, when I was part of that, patients had a two-week external trial, and if they did not respond to the therapy, if they didn't have a 50% reduction symptoms, they did not get the IPG placed, and they were exited from the trial, so those patients were not included in the analysis, in the data analysis. We actually included those in our data analysis. We analyzed the data as treated, so all 129, and then the completers analysis, and we'll go through that, and then the other efficacy outcomes that we previously mentioned. So the vast majority of our patients were female. The average age was 59, and 42% of our patients were over the age of 65 or equal to or greater than 65 years of age. The average BMI was 32, and unfortunately, 61% of our patients had a BMI of greater than or equal to 30. When we look at the baseline symptoms, this was a fairly affected patient population. They had 5.6 leakage episodes per day. Remember, to qualify, they had to have four leakage episodes on that three-day diary, but had about five and a half leakage episodes per day. All urinary incontinence was 5.8, which meant we did a really good job in screening out those patients with mixed incontinence, again, not having a lot of patients with stress symptoms in this. So this is approaching, really, the severity of the condition that we saw in the ABC trial and the Rosetta trial. And what we saw at two years was 93% of the patients had a greater than or equal to 50% reduction in urgency incontinence symptoms, and we haven't seen a response like this in any other neurostimulation trial. And if we look at the horizon from the six months to one year to two years, we see consistent response. So with that six months in the completers analysis, so those that actually were seen for evaluation versus those as treated, all 129, we can see very high response rates here. Now, as we look at the two-year horizon, the 93% response rate was in the completers analysis. So at that two-year mark, we had 121 of the 129 patients still in the trial, so a very high retention rate. But remember, this included some of the patients who actually were considered non-responders at that one-month period of time. So now we're seeing a 93% response rate. If we look at the as treated, again, with the denominator being the 129 patients, we're still seeing an 88% response rate. So again, a response rate much higher than we've seen with any other clinical trial. We see the reduction in urgency incontinence episodes from baseline being at 5.6 down to one at two years, so a pretty significant reduction in the number of incontinence episodes. And when we look at the magnitude of response, this is something that is really, I think, very important to be aware of. We see that 37% of the patients are actually dry, but 54%, so more than half of the patients, have a 90% or greater reduction in symptoms, and 82% of the participants have a 75% or greater reduction in their urgency incontinence symptoms. So this is something, when we think about the magnitude of the response, this is very meaningful for patients, because most of the time, patients will say, you know, what is meaningful for me? If I can go from, you know, four leaks down to one leak per day, if I can wear, you know, just, you know, not wear four pads, but one pad, having that 75% reduction is very, very meaningful for patients. So again, this magnitude of response is something we haven't seen in other clinical trials. And we also saw a significant reduction in the Cleveland Clinic fecal incontinence score. So at baseline, 42 of our patients, or one-third of the cohort, actually, you know, had dual incontinence. They had a score of six or greater, with the average score on the Cleveland Clinic fecal incontinence questionnaire of 9.3. If you have a score of six, it's mild incontinence. If you get to a score of nine, it becomes more moderate incontinence. So you can see that we had a patient population that had primarily moderate fecal incontinence, and that significantly reduced to a score of less than four at two years. And then in our own questionnaire, we asked, are you satisfied with your bowel symptoms? 82% said that they were satisfied. One of the things that I mentioned was that 42% of the patients had, or were 65 or older, and that one of the concerns from our study investigators was whether or not patients that were older were going to have as good a benefit, or were they going to be able to use their device. So we actually dichotomized the data into those greater than 65 and those less than 65. We saw no difference in the outcome, and we saw no difference in satisfaction or the usability with their charging. When we look at satisfaction overall, very high satisfaction with the therapy at 94% and 93% would undergo the therapy again with the same expected results. And remember, again, this is of those patients, those 121 that were still in two years, 113 were actually considered responders at that one month, which meant 16 of those patients were considered non-responders, but yet we see that 93% are satisfied, which tells us that, again, there's other factors that are driving patient satisfaction. And many of these patients who are reporting satisfaction with the therapy would undergo that again, would actually have been exited from the trial because they didn't meet that 50% improvement at that one month. And we're seeing sustained satisfaction over time from that three months out to two years, so we're not seeing any decrement in patient satisfaction. Also with the charging experience, again, 94% said it was the frequency and duration was acceptable. And remember, this was our first generation neurostimulator where the charge interval was once every two weeks, and now we have, again, that once a month to once every two months. 91% said it was easy and 98% of the patients were charging seven days or even less frequently than that. Again, the charging experience was also maintained over time. You can see that there was no decrement or decrease in the patient's experience. And looking at the safety, we do see a very high safety profile. You can see there were no serious device-related adverse events. We only had one incisional site infection that happened at three weeks, and we really had only one lead migration as well as one lead fracture. These are the, again, looking at the safety profile, we see a very low revision rate of 5% and a very low explant rate. And if you look at the explant, we did have the one patient with a surgical site infection. We had one device and a patient who had unrelated pain, but wanted her device removed. And then only three of the 16 patients who initially were considered non-responders to the therapy, only three actually underwent an explant because of a lack of efficacy or insufficient response. We did have, again, some learning opportunities. We did have one patient that had a revision due to pain. This was after she had undergone an abdominoplasty, and of course it changed the site of the neurostimulator positioning. And because of body habitus, we had some of the neurostimulators in two of the patients rotate a bit and made it a little bit more difficult for them to charge. And so we are teaching a specified standardized approach to neurostimulator placement and subsequently have mitigated that issue. So again, concluding, this result was a very robust response with a reduction in urgency incontinent symptoms in 93% of the implanted patients. Again, 90% of the patients sustained therapy rates over time, a very high safety profile, and nine of 10 patients would undergo the procedure again and deem the charging experience to be easy and acceptable. I'm going to apologize there. I think that I ran a little bit over time, but I would be certainly happy to answer any questions. Thank you so much, Karen. That was awesome. Having been doing a lot of exonics, I think it's a wonderful system, and this just sheds some more light on everything. I think we have time for maybe one question, and the question I have is, can you speak a little bit to the the tips and tricks that you can offer for PNE? Yeah, I think in going back historically, I got trained in neuromodulation back in 1998, so that'll tell many of the listeners how old I am. And at that time, we weren't doing it with fluoroscopy, so I learned with bony landmarks. And so we teach it both ways. We teach it to do what they call a blind PNE, and using bony landmarks, and also with fluoroscopy. And I think one of the things is to set the proper expectations for the patients ahead of time. So during the PNE, I personally don't let my patients shower, and I inform that they are going to have to have limited activity. So I don't want them, you know, going to the CrossFit class, or, you know, doing a lot of exercise, so that they have that awareness. And when I, you know, when we're placing the PNE leads, we usually place the PNE lead a little bit deeper, because, again, it only has one electrode. We don't have tines to secure it in place. And so as we're placing our needle, stimulating, we'll drop the needle a little bit deeper. So we won't, we wouldn't recommend that at all for a tine lead procedure. But for a PNE, so we'll drop it a little bit deeper, a little bit deeper. You may have to stimulate at higher amplitude, but then you, you know, the assumption is that that PNE lead is going to migrate out a little bit during the trial period as patients are somewhat active. So that you know that if you dropped it deeper, and as it migrates out, you're still able to activate the nerve. And that's what the important, you know, question you're trying to answer is, is this patient a good candidate for neuromodulation? The way that you're going to be able to answer that question is being able to activate the nerve for that, that trial period. And I would also highly recommend that the patients complete diaries at baseline and during the trial period, because you don't want a patient to come back and say, oh, I think this is where we're going to work. Or, you know, once I get the real implant, it's going to be so much better. You want to really be able to document that they are doing better. And then, you know, during that, that period, if I have a, you know, a patient and, you know, I'm going to stimulate on the one side that I think is the best side for that, the patient's more comfortable, lower amplitudes, and she's doing well, I don't switch her to the other side. And we will drop two leads, you know, you want to do a bilateral PNE trial. I don't switch to the other side. I don't want to, you know, confuse the patient. But then also letting that patient know that they are a good candidate for neuromodulation. They've responded to the therapy. And then as you go to place the TIND lead and the neurostimulator, you may end up placing on the right side, but letting the patient know ahead of time that they're a responder to neuromodulation. And it doesn't really matter. It shouldn't really matter which side you implant on because of the, you know, the mechanism of action and the fact that it works through reflex pathways that cross over. And so that I think is an important counseling point for the patient as well. I don't know if that answered your question, if there was anything more specific. No, no, that's great advice. Thank you. So I guess on behalf of AUGS, we want to thank you so much for doing this webinar. Like I mentioned at the beginning, it will live on the website for posterity. So anybody can access it if they want to. Our next webinar will be held November 17th at 7 p.m. Eastern time. Please visit the AUGS website for that. And again, thank you so much, Dr. Noblitt. It was awesome. Thank you, Christina. I appreciate the time. Sorry, I ran over a little bit. No worries. You know, anyone has questions, they can feel free to reach out to me anytime. Great. All right. Thank you, everyone. All right. Bye-bye. Bye-bye.

webinar

Dr. Karen Noblitt

Exonix sacral neuromodulation system

urgency incontinence

voiding dysfunctions

sacral neuromodulation

innovation

constant current stimulation

Artisan Sacral Neuromodulation trial

patient satisfaction