PROCEPT BioRobotics Corporation (PRCT) Earnings Call Transcript & Summary

So I think we're going to start the meeting. Good morning, everyone. It's my pleasure to welcome you to our investor event. My name is Reza Zadno. I'm President and CEO at PROCEPT. We are a surgical robotic company with the vision to become the global leader in urology. Please review our safe harbor statement. We have a great agenda for you today from the company. We have Kevin Waters, our CFO; Sham Shiblaq, our Chief Commercial Officer; Barry Templin, our Chief Technology Officer. But we are very fortunate to be joined by 3 leading urologists, Dr. Park, Dr. Gill and Dr. Helfand, who will share their perspective and experiences in current utilization of Aquablation in the treatment of BPH and its potential in the future for the treatment of prostate cancer. We are also very excited that Barry will share data from PRCT001 and PRCT002 studies on prostate cancer. Thanks to compelling clinical data and support from surgeon and societies we were able to receive full Medicare coverage with APC Level 6 payment in 2021, and launch the product. And with the goal to become the surgical treatment of choice in BPH in 2021, and we have been on a fast curve growing in -- since our IPO in 2021. We continued with clinical data and published 5-year WATER durability data in 2022 and expanded coverage with commercial payers. For the larger prostates, we published 5-year durability data from WATER II and NICE -- we received endorsement of NICE on the international front with the standard arrangement in the U.K. for Aquablation therapy. And we also completed $150 million equity follow-on to strengthen our balance sheet and also accelerate some of our development programs. And we announced prostate cancer initiatives. And with that, we received FDA approval to enroll PRCT002 that were patients with prostate cancer that may or may not have BPH. In 2024, we continued with prostate cancer development and received IDE approval for the first randomized study in the U.S. against the prostate data meet the WATER IV. And we also received FDA clearance of HYDROS and launched HYDROS in 2024. Also, we finished the $175 million equity follow-on to further strengthen our balance sheet, and happy to say that in 2024 we report a global revenue of $224.5 million. I'm very pleased to say we have made good progress in becoming the surgical treatment of choice, and we are on pace to become #2 hospital-based receptive BPH right behind TURP and we are making good progress to closing that gap. And a few weeks ago, in Madrid, the data on WATER III were presented. That was a randomized study against a nucleation and the data showed that the similar efficacy, but superior safety to a nucleation and also in these large prostate showed 0% transfusion. Happy to say that this year, we just guided for $323 million revenue. And we expect the enrollment of majority of WATER IV to be completed. With that, I'm going to ask Kevin to give a financial update.

We're actually going to move right to a commercial update, and we're going to spend more time on prostate cancer today. So I'm going to start with a brief commercial update on our BPH business and the progress we're making and Dr. Park will follow me, and then we'll transition the topic of prostate cancer. So last summer, September of 2024, we received FDA approval and launched the HYDROS robotic system, the next-generation system for Aquablation therapy. The timing of that release was very intentional as we captured greater than 10% market share of the BPH respective market in the U.S. in 2024 and are at this pivotal time in the company's future when we need to really accelerate the adoption curve to get to the majority of surgeons. That's where the HYDROS robotic system comes into play. So the release during the summer of 2024 was with the intent of bringing the majority of surgeons onto the platform for the coming years. And you can see some of the key features, many features or some of the key features encapsulated in the HYDROS platform. First and foremost, we now deliver AI treatment planning to our surgeons. So the confidence of being able to take an ultrasound and not have to manually read it on your own, but you have now AI algorithms that are in place to help guide the surgeon to ensure with confidence that what they're seeing is accurate. We've advanced the imaging on the system as well, because that is the foundation of our success is imaging, so now this platform provides advanced imaging. The robotic reception still is the sweet spot. And this is our secret sauce on how we perform our procedure. The robotic reception continues to exist. And with the software updates that will be available on HYDROS. We actually expect that to improve over time. And then last but not least, the streamlined workflow. When you think about a pragmatic buyer, when you think about the adoption curve of innovations. This is who you're going after with a HYDROS system. They don't want first-generation technology. They want advanced technologies that are seamless, that are efficient, and that's what the HYDROS platform provides those surgeons, and that's why we expect to have great success long term, and I've already seen the early results of that with the HYDROS launch. So some of the early learnings on the surgeon side. First -- this is our first version of the software for first assist AI. With more experience, we'll have updates similar to other technologies in your life, we'll update the HYDROS platforms. They'll get better. And right now, we're already having a lot of success with the first edition of our first assist AI. The vast majority of procedures are using AI. The surgeons are relying on it. We're getting a lot of feedback. And so far. So it's been a great, great experience in the first 6 months of usage. We're training more surgeons per launch now. This was the goal. Bring more surgeons on to the platform, and we're starting to see that early success as well with HYDROS. On the hospital side, we now have a single-use cystoscope that goes along with the HYDROS platform. Why is this important? Hospitals spend a lot of money sterilizing scopes. We've now removed that burden with HYDROS. So there's no longer that need for additional cost of sterilization with the scope. There's an increased interest now from our IDNs to standardize this platform. They're seeing success with Aquablation with all of their last few years of using AquaBeam. Now with HYDROS, they see this opportunity to standardize Aquablation as their BPH treatment of choice throughout their hospital system. And now this adoption we've talked about with -- we focused initially our strategy on high-volume BPH hospitals. It was clear. Our goal is to go cannibalize this high-volume receptive surgery market. We had -- we solve an unmet need. We believe Aquablation could do it, and that's what we've proved over the last 3 years as we can go cannibalize business from TURPs, lasers, [indiscernible] prostatectomy. And now what we're seeing over the last year and especially with HYDROS is our ability to go to low and medium volume hospitals that -- these could be large hospitals, but low and medium volume BPH hospitals and get Aquablation in there and increase their volume. And last but not least, the nursing staff benefits. Simpler and quick setup. We have examples of hospitals that have now upgraded to HYDROS. And what they're seeing is we're seeing staffs that relied heavily on PROCEPT employees to set up the proceed with AquaBeam that are now doing independently and doing it from procedure 1 or procedure 2. They're taking ownership with the procedure. So when we think about surgeons being independent. It's not surgeons on their own being independent with technology, but it's also the whole operating room feeling comfortable to technology. That's what HYDROS allows us is that seamless approach to the procedure, and we're making great progress there. That all thinks encompassed in the single tower design, where you not only make it simpler for the surgeon -- sorry, for the staff but also for the surgeon to perform the procedure. So here's the installed base. I'll quickly give you an overview of what you're looking at in the bars in the chart. But really, this is a comparison of the end of the first quarter of 2023, versus the end of the first quarter of 2025. What you see is we ended with 192 systems 2 years ago. We ended this prior quarter with 547 systems. And the colors represent the initial starting point. So what were these hospitals doing for receptive BPH before Aquablation became a part of that hospital system? So what you see in yellow are those high-volume BPH hospitals and the purple, or the dark blue, is 172 there, and that is the medium volume, and then the light blue is the low volume. The strategy has always been to go after the yellow, go after the high volume. And initially, we saw 73% after the first couple of years of launch, we were at 73% penetration of our installed base is high volume. What you're seeing now is the shift because the market is shifting. This is what great disruptive technologies do is they shift the way health care is treated. And what you see is surgeons moving, you see patients moving. You see these hospitals now bringing BPH surgery to the hospital because of Aquablation, and we're hearing great success stories of not only that Aquablation being a benefit of the hospital, but this halo effect. So because of Aquablation, a surgeon is moving their procedures to a hospital, and now they're bringing urology procedures with them. Hospital executives love that. That's how you drive growth and you drive programs, and that's why Aquablation is really one of those technologies, which is very enabling for hospitals. And I think the key takeaway here is what we're seeing with these low and medium volume BPH hospitals, when they adopt Aquablation is the majority of them, the vast majority are actually becoming high-volume BPH hospitals after they brought Aquablation in. So it's not a matter of their low and medium volume and they're staying low in medium volume. They're low and medium volume and they're becoming high volume because of Aquablation. So just in summary, the market awareness has been fantastic with HYDROS. Hospitals are really owning this marketing. They're doing a lot of direct-to-consumer advertising, physician referral education in their local markets. We've got a long runway. As you saw on the last slide, we're just over 500 installs, we're 20% penetrated in the hospital market. But next year, 2026, we believe we'll also start to receive benefits of a replacement cycle. So we not only will we have greenfields that drive growth for the coming years, we'll now start to see replacement cycle tailwinds as well. Momentum with the IDNs has been fantastic. And then like I said, these low and medium volume hospitals that are growing into high-volume hospitals has been a great success as well. So with that, I'm going to introduce Dr. Gerald Park. Dr. Park is based in Kansas City Urology. One of the first robotic surgeons in Kansas City, 20 years ago, probably long time ago. 2003. So over 20 years ago has now become really a focus on BPH, started with TURP, became an expert in nucleation and he will share his experience now as becoming an expert in Aquablation. Thank you.

Thank you for having me here. I'm Gerald Park. As introduced here are some disclosures of mine. Cancer Urology Care, that's the group I'm with. We're a community-based urology group, 31 of us. A little bit about Kansas City. It's a metropolitan area about 2 million people. We're famous for barbecue, the almost 3 peak cheese. And we're also, hopefully, after this top will be famous for BPH. So BPH is something that is very common. Our group treats about 22,000 men, but we only treat them surgically about 1,600 people. It's about 7%. Cancer-wise, same thing. We treated about 800 to 900 men with prostate cancer. But in terms of definitive therapy, that means surgery or radiation about 1,000. So it is important for us to understand the mindset of what BPH is to urologists. So I'm going to give you guys a little bit of a history lesson. So BPH, as we know, has moving around forever. Prior to the 1926 is always done by open surgery. It worked great. But unfortunately, a high mortality rate, people actually died from that survey. So when 1926 came around and TRP was introduced, that's been 100 years ago, it really changed the paradigm of BPH (sic) [ TRP ]and it became the gold standard quickly. Because people aren't dying anymore from BPH (sic) [ TRP ] surgery, they were doing great. But then something happened along the way. For about 50 years, TRP had a great run. It was really the only show in town. But morbidity became a bigger issue. And a lot of those studies were actually done at University of Kansas. The leaders have thought then were in the 1970s and '80s. And they showed that the morbidity of TRP was up 30%. They get it down to 18%. And that was in the 1980s, and this is when medicines were coming on board. So no matter how good TURP worked because of the morbidity with it, it didn't take long for it to be knocked off its pedestal. And that's where medicines came along. And Medicines basically were safer. And because they were safer, urologists has got best good physicians will always take the hippocratic goes seriously, do no harm. We don't want to hurt people. Why are we harming people for a benign disease. So medicines quickly became their first line therapy. TURP is still here and became basically the backup therapy. When people can't do medicines, then we do surgery. But the reality is that medicines don't work that great. We said, you know what, maybe it's safer. It works okay, but at least we're not hurting people. But we're really not helping them either. And so now this is a prime situation where something can come and take care of this problem. And that's where Aquablation comes into play. Because Aquablation literally is that safe procedure, it's the effective procedure, and it's a great experience for patients and for a surgeon. So when I was first learning to the venture robot in 2003, I remember intuitive have always saying, "Hey, we're going to make the average surgeon good and a good surgeon great." What Aquablation does, it makes the average surgeon great. I'm going to say it makes us super human, and I'll show you how it does later on. So no longer do patients have to sacrifice safety and efficacy, we can have both. We can have our cake and eat it too. And I think that Aquablation is really don't need modality that's really going to grow the BPH model back to a surgical-based disease. Like it was in the 1970s, 1980s. And the reason I say that it needs to be a surgically based disease is we understand the anatomy. It's an anatomical disease. It's an overgrowth of the transition zone. That anatomy does not go away with medications. It stays there. Medicines just hide it. So whenever I look at things, I always tell my patients come and see, where I'd tell my fellow colleagues seat, SEE, look at safety, look at efficacy and look at experience. So safety, we always look at first, do no harm. Efficacy, we want to help people. We also want a great experience for the patient and for the surgeon. TURP is a historical gold standard because it was efficacious. It worked great. Not that great, not that safe. Not that great in experience for the patient or a great experience for me either. So medicines came along, knocked it off, became the first-line therapy. But the thing about medications as people are living longer and longer as the Wall Street Journal said last year, this baby boomer generation is healthier and wealthier than ever. And so because of that, they want a lifestyle that doesn't slow them down and medications slow them down. Because a lot of them are on polypharmacy, there are multiple medications. We get these interactions at a patient, the day who said, "Hey, I fell why am I on this full MAX." Hey, let's stop it. let's get you to definitely take care of this. The other thing is bladder health. Medicines do not protect the bladder. There's two things in the body that pump fluid. The heart pumps blood so you can live and the bladder pumps your urine out, so you're comfortable. And so we want to do these things to make sure that pump lasts for your lifetime. So now Aquablation is that new gold standard that I believe can do accomplish both for us. Safety, efficacy, experience for patients and experience for the surgeon. And I think the data that we're seeing from our group proves it. So here's the data. Here's our group. So 2021 was a year prior to Aquablation. We're doing about 1,100 cases. So statistically, that's about 5% conversion rate. We got the robot in 2022, Q4. So really it's 2023, 2024, when we really adopted Aquablation, started with one surgeon, me. One hospital, one robot. And then quickly, within 2 years, we now have my 31 fellow urologists, 15 of us are doing it. When I was in enucleation, I was soundly alarm. This is the greatest surgery ever, try it, try it and try it. I grew in 10 years from 1 surgeon me, to 2 surgeons in 10 years because the adoption curve is that hard for enucleation. Aquablation, 1 surgeon, 2 years later, 15 surgeons. This adoption curve is what enables to neurologist like myself, who don't have time to do these extended fellowships, take 3 months off, 6 months off to learn these new technologies, we can immediately embrace this brand-new technology and make us super human in how we can treat BPH. So I see these receptive therapies is basically going away or being very niche type of procedures and Aquablation is going to be that workhorse, of what TURP was in the '70s and '80s. Back in the '70s and '80s, all old people knew they're going to get cataracts, if they're a women they get a hysterectomy, if they're man, they get a TURP. And I think the day is going to come in the very near future as men get older, they realize, you know what, I get my cataracts done and I get my Aquablation. It's just power life. And I think that, that's the way we're going to see how Aquablation is going to change BPH. Now we'll dial-in on my personal practice. So I was kind of the enucleationist in our group. I did all the big glands or hard glands. And so I was about 100 cases a year, 70% of being enucleation. And then once I start doing Aquablation, I quickly doubled my numbers. I actually grew at 124%. But the superhuman part that I'm talking about is I did this in the same time frame I was doing previous. I wasn't working more hours. I wasn't working more stressful. I was actually, if anything, I was getting home earlier. Because I'm able to do these surgeries in a super human way that it cannot have done without the Aquablation. And enucleation it would easily take me 1 hour, 2 hours, sometimes 3 hours to do surgeries at the Aquablation lets me do in like 40, 45 minutes. And so the question is, how do I get so many people to do surgeries? Well, it wasn't that I got people do surgeries. I just showed them the problem. And once you show people the problem, you show them data, they immediately make the right decision. So before 2020, I was the typical urologist, your patient will come in, hey, you do it all right. Yes, I'm okay. All right. Here's to refill see me next year. And that's how I would do. And next thing you know, we're in that crazy cycle, and that's why 97% of people are treated with medications because it's really simple. You say you're okay. I'm good. You know how guys are. Are you good? Yes, I'm good. move on. And -- but what I realize is if we show men what's really going on by working them up, and this is something that AUA has given us these guidelines. And they said, before you do surgery, you should evaluate them. But what I realize is changed it not until I already made a decision to do surgery. I said, you know what, let's do a workup and then decide if you need surgery. The fact that they show to the urologist obvious means I want help. I want something done. And so I did is doing pressure studies. I do have volume studies. I do cystoscopy. And all of a sudden -- and we have a nice screen. And when patients see their prostates enlarge, they see a median lobe, they see trabeculation, they see bladder damage. They're like, "Oh, I need something done." They realize, "Hey, is an anatomical disease, Hey, my prostates enlarge." And so I never have to convince anyone that they need surgery. Men are already self aware that, "Hey, I have a problem. I just don't know what it is." I show them on the screen. They're like, all right, let's take care of it. And I had to admit I learned this from my mechanic. My mechanic, every time I go get my oil change. He does that free check up for me. And he goes, so just say, "Hey, you want your air filter changed, $50? I'm like, I'm fine. It doesn't smell my car, I'm good." But now what he does, he brings the air filter out. It shows me this dirty air filter and says, "Hey, you want to change this? I got absolutely. Look how nasty that thing is." And that's what we're doing for our patients. We're showing look at your prostate. Look at what it's doing to you. And you're like, you know doc, lets get something done. And once I get into options and they know that resected therapy is the 100-year-old proven modality, I want that tissue removed. But I want the 21st century way of getting it done. I want the Aquablation. And patients are coming to me for it. So the secret sauce for me as -- so we establish how to safe, we establish as effective. Now it's the third -- the third for me, the experience. The experience for me is the efficiency. That is what separates this anything else. And you can see these curves on the left side, it's basically these different modalities as prostates gets bigger, takes more time. With Aquablation, it's relatively flat. Now these are my numbers on the right, and you can see 60 minutes. Pretty much all my cases, no matter how big they are, will be finished in 60 minutes. I love it. My schedule is predictable. I know that I can get to offense in time. I can get to that meeting in time. I can get to dinner in time. I can do all these things, and I can plan my day and be very efficient with my day. And so you can see how I can stack cases. I can plan on doing 5 different cases of all varying sizes from 77 grams to 142 grams, and now be on average about 40 minutes. And this is what I say is superhuman. I think as a non-urologist you see this, 142 grams he did a surgery in 40 minutes. Okay. It's a nice number. But the reality is it's something that is literally superhuman. So it's like in the Boston Marathon just happened and the winner was like in 2 hours and 2 minutes, and I was like, wow, that is amazing. No way I could do it. But if I told you, hey, I ran a Boston Marathon in an hour, you're like impossible. And I said, well, I did use an electric bike. So then you're like, "Oh, that's how you did it." You leverage technology, you leverage what's in front of you to accomplish the same goal and that's what Aquablation is doing. It lets us be the superhuman surgeons and do things that physically cannot be done without this robot. So with this excitement that I have about how I've seen the robot take effect with BPH, I'm super excited about WATER IV. And can we use the same very safe, very effective technology and use it for cancer? And because for prostate cancer, again, I think we have that same that SEE safety. I'm really wanting to know, are we going to do a harm reduction. Are we really going to help these patients in a safe way? I also want to know the efficacy, how is it going to work? What's the retreatment rates? Of course, we don't want to see anyone have any increased risk of metastatic disease, things of that nature. But the last E is experience, what's the patient and surgeon experience? Is it going to improve the quality of life of people? Is this something that guys are going to say, you know what, as you saw from my first graph, we have around 8,900 men with prostate cancer, only about 1,000 get treated. What's happening with all that 7,000 people because prostate cancer, and you'll hear later, is one of those cancers, acts as a slow-growing cancer that we don't always have to sound the alarm. But at the same time, patients don't quite feel comfortable, I get cancer, and we're just going to do nothing about it. So I think prostate cancer is one of these things, where Aquablation has a real early chance of making a real big dent in it. I kind of equated to what lumpectomy did for women. Back in the day, when I was a medical student, I remember there was a lot of controversy. It used to be, "Oh, there's cancer, radical mastectomy, you got to get rid of it. But then people start thinking do we have to. And I remember the first people who were saying lumpectomy, lumpectomy. They're like, boy, I don't know about that. But now it's been proven that for low-stage breast cancer, that is the treatment of choice. So lumpectomy has led women stay women, and I think, Aquablation will let men stay man. Thank you.

Thank you, Dr. Park for that introduction to the prostate cancer section. I'm going to go through a little bit of the why. Why is PROCEPT tackling this challenge. And I call it a challenge because it is a massive undertaking to change the way we think and ultimately treat men with prostate cancer. I'm going to walk you through that. So the journey of a prostate cancer patient, unfortunately, is very different than almost every other cancer that's diagnosed. And so we're going to talk you through why it's different and how a patient about their treatment options, better diagnosed with prostate cancer. It's also important to understand that prostate cancer is a multifocal disease. And so we're going to walk you through why focal treatments for all of the right reasons, have been trying to make an impact, but are struggling to make an impact prostate cancer is a multifocal disease, we're going to talk about that. We'll give an update on the clinical data. We've done some great work in PRCT001 and PRCT002. The intent of 001 and the intent of 002 was to prove to ourselves that we could do this. And so, now we've started prostate cancer WATER IV prostate cancer study to show that we can actually do this and we're going to prove it through that study. And then last but not least, Dr. Health is going to come up and talk about the Aquablation therapy cancer technique, very different than the BPH technique. I think there's a lot of confusion out there as to this is not going to work for prostate cancer. You're right, if you think the BPH technique is what we're going to do, but we're not going to do the BPH technique. We are going to do a cancer technique, and we're going to talk you through that as well. All right. Let's talk about the incidence rate for prostate cancer in the U.S. Prostate cancer is the most diagnosed cancer for men in the U.S. outside of skin cancer. All right? And you see the annual incidence of 300,000 procedures. I've got the blue highlighted because localized cancer is what we're going to focus on. Localized cancer means it has it spread outside the prostate, that's what Aquablation is going to focus on. As 70% of diagnosis every year of localized cancer. But think about the risk factor, all right? When you think about all of these cancers that are diagnosed, they get graded into low, intermediate and high risk. And we're focused on the low and intermediate risk patients. There are 76% of cancer is diagnosed as low and intermediate risk. We'll talk you through what gets done if it's high risk, but our focus is on low and intermediate risk. So a large incidence of patients. But I think what's really, really interesting is that there are over 3 million men in the U.S. alone that are living with prostate cancer. And so let's talk about why that number is so high and why there continues to be an unmet need for these men? Dr. Park just talked about breast cancer. He actually stole my example. That's okay. That's okay. Because what you see here on your screen is lung cancer. You see colon cancer, you see breast cancer, you see skin cancer. All very highly diagnosed high incidence rate cancers and all treated with the goal of being able to not have to remove the whole organ. How can you treat this in a way where you don't impact the quality of life? You minimize side effects you minimize complications. And breast cancer is a great example of that. And I want us to think about prostate cancer and the opportunity the same way mastectomy has transferred over to lumpectomy. Mastectomy still happen, if it's a high-grade disease or aggressive cancer, you unfortunately have to get a mastectomy. But if you go to a Breast Cancer Society meeting, what you see is the talk has shifted over the last 5 years. It's not a matter of can we treat the breast cancer. It's a matter of survivorship. How do we treat the cancer and keep the woman whole? Improve our quality of life, these are young women and young men are getting treated with or getting diagnosed to prostate cancer. There's an unmet need there. So the question is -- we've all had loved ones, maybe some of us have been diagnosed with cancer. And when you get diagnosed with cancer, what's the first question you deal with is, how do I get it out? When do I schedule surgery? How do we treat this? That's the first question, but it's different for prostate cancer. Unfortunately, it's different for all those millions of men. And the reality is the question, if you have a lower intermediate cancer isn't a matter of how do I get it out because when you provided the options, the trade-offs are massive. Impetus and incontinence for a young man is massive for a man of any age. And that's the trade-offs you have to talk about. And so now you start thinking about, not do I treat it, how long am I willing to monitor the cancer progression? Because now it's a matter of watching the cancer progress. And do I catch it fast enough to treat it? And what am I willing to give up? Because I'm going to treat the cancer. I know I'm getting something up to my lifestyle. Something has to give. And that's what you think about if you're a prostate cancer patient today with the options that are available to you. So what's the goal? I'm now a prostate cancer patient. I go through this journey. I'm speaking to one of the surgeons on the stage here. And the goal is how do we have your lower intermediate risk and in the conversation is how do we avoid this cancer from progressing? And if it does, how do we safely intervene early in this progression, okay? So I have an initial diagnosis on the patient, and we have this thought process. I have these risks that far outweigh the benefit at this stage because I have lower intermediate-grade cancers. So I'm told we have this ability to go on active surveillance. Active surveillance doesn't mean you don't do anything. You come back, whether it's MRIs or biopsies or PSA checks. There are different things at different time frames that you have to have happen to become an active surveillance patient. So the surgeon now, they also have to consider, is this patient reliable. Is somebody is going to come back and be treated. What if they move, they have to find a new surgeon. There's a lot of thought process has to go in just being in this active surveillance protocol. And really, the goal here is we're going to avoid over treatment because over treatment means we lose those benefits and it becomes a risk. But here's what happens. At first follow-up, typically about 1 year, 1/3 of those patients, that cancer isn't the same condition as when it started. It's already gotten aggressive. 30% a first follow-up the cancer has progressed. So now I'm a patient -- and I'm like, all right, I've now made this trade-off. I'm going to live with cancer, but I think I can do this. And within 1 year roughly at the first follow-up, 30% was men are already now saying, "Oh no, what am I going to do?" So now you have this decision you have to make. You need to consider intervention. Do I want these trade-offs because the benefits, meaning I'm able to survive potentially because it could now take my life, do they outweigh the risks, which are erectile dysfunction and incontinence as the 2 primary risk that go along with prostate cancer surgery. So now you have this decision you have to make. And then when you start thinking about the decision process, you say, both happens? What happens if I continue to surveil this cancer? Well, now what we know is that when you begin active surveillance, 60% of these patients will eventually move to radical surgery. The majority of them end up getting surgery. And I'm talking about radical surgery, meaning radical prostatectomy or radiation and that's where these massive risks come into play. So the question isn't whether or not that radical surgery on the table for you. It's a matter for most men, is when is it going to happen? And so that's what goes through the mind of these men when they're going through this process of having prostate cancer and the journey they go through. I'm going to take you a step back and tell you about PROCEPT and why we're on this journey and what we're trying to achieve. So this is our avocado slide we show for BPH. Many, many years ago, we started this journey on BPH. Why did we start this journey? Because in the world of BPH, there was an unmet need. Receptive surgeries have been around. Dr. Park has talked about it, TURP has been around for almost 100 years. And what we know about receptive surgeries and proven time and time again, whether it's a laser procedure, whether it's TURP, whether it's simple prostatectomy is it worth, it's effective, it's durable, but there's a trade-off in the form of a ejaculatory dysfunction in the form of continence. You have to consider that this is an elective procedure. And so because of that, non-receptive surgery for over 25 years. There's been a whole host of them and more coming out, how do we fill this void, the void of safety? And so what they've been able to do is provide an option which is safe. But unfortunately, there continues to be this trade-off because if you choose safety, you're giving up what, you're giving up efficacy and durability. And so that's what Aquablation has done. We've come to market, we bridge that gap. That's why we're having the success we're having, Dr. Park just talked about it is you can now have a conversation with a patient for an elective procedure and be able to have a conversation about not having to give up necessarily safety for efficacy and durability. Now think about prostate cancer. The story is not that different. It's a very different disease. We're talking about cancer now, but the story, the unmet need is still very similar. Now instead of size of prostate or shape of prostate, we're going to talk about progression. Progression of prostate cancer. And what you see here is Grade Group I to great Grade Group III represented. So as the cancer gets more aggressive from low risk, to favorable intermediate risk, to unfavorable intermediate risk, the options begin to change and the conversation changes with the surgeon and the patient. And when you think about low risk, you may think active surveillance. But what we actually see as many of these patients actually get prostatectomies. They're getting radical prostatectomy in their low-risk patients because they don't want to live with cancer. And when you start to move to a favorable intermediate and unfavorable intermediate, you're starting to see radiation and prostatectomy start to step in, and that becomes a primary option for those patients. So what are we trying to do here with Aquablation, it's the same story. When you get radical therapy, you know you're treating the cancer, you're getting the cancer out. That's the goal. But a erectile function and continence becomes the trade-off. On the other side, you have active surveillance. What's active surveillance trying to do? Well, it's not treating the cancer, you're surveilling it, you're watching it, you're monitoring it. But you're prioritizing the quality of life, sexual function and continence. So that's the current paradigm. That's what's going on with the world of prostate cancer. When you think about Aquablation, you think about our ability to prioritize both safety and our ability to treat cancer. That's what we're trying to achieve. This has been going on for many years in the world of prostate cancer. You think about focal treatments, you think about what they're trying to do, it's the same story what they're trying to do, but how they go about it is not how we go about it. Focal treatment is very different, and we're going to create a new category of surgery and prostate cancer. So think about focal treatment. This right here is an MRI with a visible lesion. So your yellow is your visible lesion, you found an MRI. For the late person, great, MRI is like, that's what you use. So we saw it, let's treat it. Okay? But here's what we know. What we know is when you see it and you treat it with prostate cancer, it doesn't mean that's the only cancer that exists. And in fact, UCLA did a study, and what they showed was that focal disease prostate cancer is not a focal disease. So 40% of these men that had Grade Group II cancer, when the pathology was taken after the lesion was removed, they found cancer on the other side of the prostate. Cancer that was missed by MRI. Cancer that was missed by biopsy, but it was there. So when you think about focal disease, when you think about focal treatment, there's a reason why it continues to struggle to have the success it needs to have is because prostate cancer is not a focal disease. And when you look at the studies of focal therapy many times, what they're doing is they're measuring their success of treating the lesion to look at that yellow -- the yellow circle. These studies show my success in treating the yellow circle. But when you think about the patient, you're not treating the whole gland. So you may still have cancer. So when we think about our results for PROCEPT, and we think about Aquablation is going to report out. It's not apples to apples. We're talking about success of cancer-free patient, not success in treating one lesion, very, very different. The other question, I think we need to understand is the difference between BPH and the difference between cancer. This is the transition on the prostrate. When you're treating BPH, what are we trying to do? We're trying to put a big old tunnel right in the middle of a transition zone. We're just putting a big whole chunk of tissue or taking it out and are basically allowing the bladder to empty. That's all we're trying to do. That's the most important thing is emptying the bladder. All right? This is very different. When we think about cancer, you need to treat the peripherals on most cancers exist in the peripheral zone. What we're going to show you today is that we can do that. Okay? We haven't had to try to do it. We didn't want to do with BPH. Okay? So being able to do it versus the desire to do it are very different with cancer, we'll treat the peripheral zone as well. So in conclusion, prostate cancer is a multifocal disease. It requires a whole gland treatment, and that's what we're going to show you today. Based off our PRCT001 and 002, we have strong confidence in the design and the assumptions we made in WATER IV. We're excited to continue enrolling these patients and show you data on that. Aquablation therapy can treat the peripheral zone. We'll talk about that. And 60% of these patients on active surveillance will progress to radical treatment. And that's really, really important takeaway. So we're the first company ever. We're very proud of this, and we hold ourselves to a very high bar. This company is built on level 1 clinical data. We're going to do it again with WATER IV PCA. We're the first company ever to receive an FDA IDE approval to enroll this randomized trial comparing our therapy versus radical prostatectomy. There are other studies out there, but they're not FDA studies. We're holding ourselves to the highest bar possible. And that's really, really important to differentiate as well. And we're going to pursue a specific treatment indication. That's long term. There are other things we can do in intermediate, but we're going to go after a treatment dictation as well for prostate cancer. So with that, I have the pleasure of introducing Dr. Inde Gill. Dr. Gill, I crossed path with him 20-plus years ago, when I was a sales rep. He was at Cleveland Clinic. He was running circles around people. Being an early adopter at that time. And he hasn't slowed down at all. He's now the Chair of Urology at USC and I have a pleasure of having him as our primary investigator for WATER IV. Thank you.

Great job. You laid it out beautifully, Sham. Thank you. Just as I start, I have no -- I'm not a paid consultant for PROCEPT. And the 2 conflicts of interest listed here are companies that -- start-up companies that we've done, but I'm not a paid consultant. When we talk about prostate cancer, you often hear the word over treatment. And you'll also hear that low and sometimes intermediate risk prostate cancer does not need to be treated. These are generally accurate comments, but there are nuances. What is over treatment? Overtreatment more reflects the nature of the treatment rather than the nature of the disease. If treatment were as simple as just scraping off a mole or taking a little polyp on colonoscopy, we won't be talking about overtreatment. The problem is for low and intermediate risk prostate cancer. The treatments that we have are somewhat heavy handed and have sequela life-life -- lifetime sequela that decreased their appeal to men with low and intermediate risk prostate cancer. So what is low-end intermediate risk prostate cancer? It is dependent upon the amount of cancer in the prostate. It is dependent on whether the cancer has spread outside the prostate. And what is the cellular level aggressiveness of that cancer. So these 3 things determine the low intermediate high-risk scenario. And essentially, the intermediate risk is divided into favorable intermediate risk and unfavorable intermediate risk. For the -- how do we assess stage? We assess stage by figuring out whether the cancer has spread outside the prostrate. How do we assess grade? Grade is looking at under the microscope at the cells and assessing their level of aggressiveness. The least aggressive is Grade Group 1, the most aggressive high risk is Grade Group 5. And PSA is a surrogate for the aggressiveness of the cancer. So that's how we figure out whether cancer is low, intermediate or high risk. So going on to treatment. Looking at the low-risk cancer Grade Group 1, it is very straightforward. Active surveillance. Looking at the high-risk group, Grade Group 4 or 5 is very straightforward. We are -- this is coming at us. We are going to throw treatments at it, i.e., radical prostatectomy, radiation, et cetera, to neutralize this. It's the vast intermediate part that is Grade Group 2, Grade Group 3, where the conundrum lies. So I mentioned active surveillance for low risk. What does active surveillance mean? Active surveillance means that we are not going to do any active treatment right away. It doesn't mean we are not going to do active treatment at all. It just means that we are not going to do it right away. Active surveillance. We are not taking any anticancer steps right away. So the game plan here is the man has been diagnosed with low or intermediate risk disease. We are going to continue to do PSA checks every so often, let's say, every 6 months or so. And then we are going to do MRI and then we are going to do maybe a biopsy at a year or 2 or something like that. So that's how we follow patients along on active surveillance. And in this continued surveillance, if the cancer takes a leap, if it goes from low to intermediate risk, then our thinking changes. Or the man could say, I'm stressed with the fact that we are just following cancer. I want to do something about it. So when that switch occurs is when the dam burst. That's when we go from having a good lifestyle now to having active treatment, which is radical prostatectomy or surgery. And that's where then the sequela of these treatments, which is essentially urinary incontinence or issues with that and erectile dysfunction, they kick in. For intermediate risk disease, the guidelines do not give a preference between active surveillance or radiation or surgery. The overall message here is we do not have enough prospective randomized data to be able to guide you strongly one way or another. And so for intermediate risk disease is between the patient and the physician as to which way to go? Active surveillance, radiation or surgery? So how do we figure out which way to go? The -- one of the best trials is the PROTECT trial. This is from the United Kingdom, run by Oxford. And this randomized about 1,600 men equally into active surveillance, into radical prostatectomy and radiation therapy. This data were actually quite stunning to guys like me, okay? A major finding was that at 15 years, if you just did active surveillance for men with low and intermediate risk disease, their chances of dying from prostate cancer are really not a whole lot different than if you actually did surgery, or radiation. Meaning the difference in prostate cancer-specific mortality in low and intermediate risk men undergoing active surveillance and followed for 15 years, the difference in cancer-specific mortality was less than 1%, 0.9% compared to if you did surgery or radiation right away. Well, that sounds pretty amazing, right? I mean, all we are doing is doing surveillance and the patient is having an excellent mortality outcome. But it's obviously not as simple as that. There are nuances as is often the case within this. In this trial, men on active surveillance initially did not have surgery or radiation. But as they were followed, then cancer progressed then they moved on to getting the radical treatment. And that is when the sequela of the radical prostatectomy or radiation kicked in. So in this instance, at 15 years, 60% of men, 60% had switched over to active treatment. And so the excellent cancer-specific outcomes were reliant on this conversion to radical surgery. Ideally, for active surveillance, it would be that, the man is on active surveillance and does not have to have any treatment. And would die from a non-prostate cancer cause. That would be a home run. That occurred only in 15% of men at 15 years. The vast majority had to have either active treatment or died from other causes. So as I'm saying that these men who are now going to go to active intervention, that is a heavy-handed approach. These men with low-to-intermediate risk disease are now going to have a sequel of treatment, which is incontinence and erectile dysfunction and a kinder, gentler software approach is what is needed. And Aquablation, I believe, is that approach wherein the goal is to go in from inside the prostate and to be able to sell out the entire prostate not just the obstructive tissue, but the entire transitional and peripheral zone and be able to, thereby eliminate the prostate cancer without hurting the neurovascular bundle that runs outside the prostate or the sphincter that is outside the prostate without harming these 2 critical structures, we are thereby able to take care of the cancer, while minimizing the downside, the morbidity. There is diagnostic uncertainty of prostate cancer, and this is substantial. Firstly, as Sham already said, prostate cancer is multifocal. All residents learn it literally in their first year of training that 80% of men with prostate cancer are going to have multiple spots within the prostate of cancer and typically 2 to 3 spots, okay? So that is a multifocal disease, which we are now trying to take care of with focal therapy. So there's an inherent contradiction there. 40% of men diagnosed with Grade Group 2 disease on one side, actually have disease on the other side as well, unbeknown to us. Active surveillance studies show that if a man has had his first prostate biopsy we want to typically reconfirm it. If we're going to do active surveillance or focal therapy. The guy has a first biopsy, then we reconfirm it with the second biopsy. The second biopsy increases -- upgrades the disease in 30% of men. So again, doesn't inspire confidence in the biopsy itself. Focal studies have shown what intermediate risk disease about a 30% consistent failure rate, either infield recurrence or out-of-field recurrence. And it is this diagnostic uncertainty that supports whole gland treatments, but the problem is the whole gland treatments have high morbidity. So we feel that -- or I feel that Aquablation has a niche that it could fulfill, which is currently lacking. Focal treatments currently are thermal, okay? And there are other sequela from thermal treatments. Aquablation has the -- and because they are thermal, therefore, they can hurt the neurovascular bundle, which is outside the prostate. So therefore, we typically restrict thermal treatments only to 1 lower with the prostate. We don't do Bilobar. If you don't do Bilobar, you're going to leave disease behind as we are showing here. So therefore, Aquablation, which is athermal and can take care of both lobes from the inside of the prostate is therefore appealing. We are embarking on the WATER IV study. This -- I personally feel is going to be a game changer. Never before in the United States has a new treatment being compared to an established standard in a prospective randomized manner never before. And it's been really my privilege to have been involved in the design of this study. I'm eagerly looking forward to it. I feel that Aquablation has the potential to be able to address the issue without causing sequela without nuking the entire neighborhood. And as important as it is to show the efficacy of Aquablation equally important, and I cannot stress this enough. Equally important is it to show it in the setting of a prospective randomized trail. If it is just a single-arm pilot study, it's not going to carry the day. It is just not going to get into guidelines. It is not going to be recognized by payers. And therefore, will not impact urologists like me who are looking to that level of acceptance in the guidelines, et cetera. The trial that we've designed, I feel is innovative. FDA has blessed it, and we are already underway. We feel that we will not only get this done for the first time in the United States, a prospective randomized trial comparing a novel treatment to established standard, but we will get it done in record time. We are holding ourselves to it. We are already underway. It's 280 patients, randomized 3:1, and we hope to be able to conclude this trial. I'm told not to give the number, but I'm trying to hold back, but we're going to get this done in short order. Thank you.

Thank you, Dr. Gill. Always a pleasure to hear you speak. Okay. So I'm going to get into the data from the 01 and 02 study. And to be clear, this is not data from the WATER IV trial. The study is undergoing with enrollment right now. So we've used the last couple of years to really hone in our understanding of our data, how the procedures evolve to treat prostate cancer. Dr. Helfand is going to go into that. So I'm going to show for the first time our outcomes data from the patients that we've studied to date, and then we'll get into how we and what we've learned about the procedure. So PRCT001, it's a global trial, single arm. We've enrolled about half of that study to date. It is still on going right now included man in Grade Group 1, 2 and 3. The PRCT002, remember, was a small U.S. feasibility trial that completed last summer with 22 patients. We are combining them and pulling this analysis because we now have 88 patients treated, 65 with 3 months follow-up and 47 a 6-months follow-up to give the full picture of data that we have. So if you look at the demographics, typical localized prostate cancer. Men average age 67, 3/4 were enrolled in the United States Centers across the 2 different studies. 70% had intermediate risk with the vast majority of those being Grade Group 2 disease. We've kind of moved down the table there. 80% of men had an MR visible lesion. So I mean it's about 20%. We're just detected on systematic biopsy. The group had moderate BPH, which you can see there is an average score of 16. As a reference point, a typical BPH trial will be 21, 22 points at baseline. So some lots, but this is not a BPH trial per se. When you get into the anatomical details, the average prostate size was 61 grams. The largest size we treated was 133. Prostate cancer tends to be small glands than what we see in BPH. BPH. We've treated a gland over 1,000 grams cancer, they're going to be smaller. Where the cancer was located as both Sham and Dr. Gill noted, 3/4 was in the peripheral zone. And you can see here, there was transitions zone only in a quarter. There was a transition zone and peripheral zone and then peripheral zone only. Moving down to the procedure details. The procedure just took over an hour of time. Length of stay was 1.5 days. The surgeons have not been rushing for day case surgery. It is something that is feasible, but that's not a priority of the study. Catheter duration about 2.5 days. And probably most importantly, there were no transfusions reported in these first 88 cases, even with the more aggressive removal of tissue in the gland. Okay. As we've touched on the design of the trial and reference points, these are 4 of the most contemporary, probably credible publications in the field of oncology -- prostate oncology today. And we've used this data to help create the assumptions for the statistical design of the WATER IV trial. We're also using these as a reference point to compare the data of our data today as we walk through this. So to start, this is the radical prostatectomy arm of the PROTECT study. It's roughly 500 patients. And this measurement is something called the SHIM score. This is a patient-reported outcome tool meaning they have 5 questions to answer. The maximum score is 25, and they have great erectile function. And if you have 0, you have very poor erectile function. So the group, on average, had an average score of 16 at baseline. At 6 months, the group on average dropped just over 4, and there was a bit of recovery at 12 months at 5.5. How does this measure up to the scale? So somebody is considered to have severe ED of a 7-point or less SHIM score. So you can see the population ended up at 6 months in the severe category, and you can see there a band from roughly 8% to 11% for moderate ED. A second study, the [indiscernible] study, a large study done in France. They reported just baseline and 12 months in their data. And you can see similar numbers here at the average starting at 19, and the resulting number at 6 at 12 months, and you're again in that severe ED category. Now the Aquablation data. So our combined data, we started at 17.5, and we went to 17.1 at 6 months. So there's no change. We're not reporting 12-month data today because we don't have it yet today. The population needs to age as we follow these patients over time. So remember, our first regulatory endpoint is around erectile function. And our comparator arm is the radical prostatectomy arm. So this is a clear indicator as to the -- how we've designed our study, excuse me, and what we have modeled in. So these numbers are in very good alignment with what we've assumed for the radical arm, obviously, from published data and now what we've assumed for the Aquablation arm, which is stability in erectile function. Then our other second main regulatory endpoint at 6 months is around pad use incontinence. So this is any pad use is collected. So again, we're starting with the radical prostatectomy arm of the PROTECT study. 2% of the men at baseline were already using pads that had no bearing because it wasn't caused by the surgery. However, at 6 months, you can see it almost bumped up to near 50% of the population, and then there was a bit of recovery were only about 1 in 4 men were using a pad at 12 months. If you look at the bridge at all paper here in the middle, again, they only reported baseline in 12 months, you can see a similar fact there, where 4% were on pads entering the trial, and you had about 1 in 3 still using a pad at 12 months. When you compare this to the data that we have now seen, we started with 3%, so very in line with the other studies that you've noted there, and we had a bump up to 8% at 6 months. Longer-term data will be reported later on. And again, as our second co-primary endpoint around pad use incontinence, again, these assumptions, obviously, the published data we're already aware of, but our data is panning out as expected and very consistent with what we see in the BPH role. Okay. Now we get into kind of the oncologic control aspect of our data. So as Sham and Dr. Gill have touched on, which is cancer is a progressive disease. And so here are 2 very good sources as to monitoring active surveillance patients and progression at their kind of checkpoint, if you will. So the number of 30% has been used. This was a study at UCL in London, and you can see it's about 1 in 3 men. The other paper from Case Western from the United States is around 46%. Our data, which is a protocol-driven biopsy across all patients was 10% in the study here. So we're noting this is an important fact as Dr. Helfand is going to show in some of his data. He has looked at this data out to 5 years in his own population and seen a lack of progression after man has undergone Aquablation. And more to that later on in the talk. This all combines to these diagnostic measures, meaning you look at MRI, you look at PSA, you look at Grade Group under biopsy. And all those factors decision between a patient and a surgeon as to, okay, do I need another treatment? Is it time? Did I need something else done? And so this is what's called often a salvage treatment. So you have your first treatment, your primary treatment. And then how often do you need something else? So these first 2 examples are both focused on radical prostatectomy from 2 different studies. And you can see at about 1 year, 6% to 7% of men will need an additional treatment following their index radical prostatectomy. It's typically radiation therapy. And they're doing this because they're watching a PSA rise, et cetera, as the patient moves on. And again, we just have 6-month data today. As expected in this field. This is why we're running a 10-year WATER IV study. We have to have long-term data with the data we have sitting on today, there has not been any salvage treatments up to the 6 months point with our patient group today. So as we know, kind of the best of the best as far as treatment is radical prostatectomy, and it's close to perfect. So again, this is the bar that we are aiming at. We are in the first 6 months off to a great start. And I think from our approach of being a whole gland treatment, we have strong belief that our long-term durability, meaning lack of salvage treatment is going to hold up in the long term. And that's why we're happy to start the WATER IV study that is ultimately going to have a 10-year follow-up. So in conclusion, our data is encouraging. It further supports our -- the design of the WATER IV randomized study that we're doing. We are seeing a material stop or delay of progression of cancer. We are seeing significantly reduced rates of unnecessary morbidity from the index procedure. And as the Aquablation arm, we have even greater confidence today and the assumptions that we've made in the design of that trial. So at this point, I'm going to turn it over to Dr. Brian Helfand. Is a -- I have my notes here. I could start this, and then there's a lot more. A urologic oncologist who's the Division Chief of Urology at Endeavor Health. He's also a professor at the University of Chicago and most recently named Chief Scientific Officer at Endeavor Health. So Brian, I will turn it over to you.

Thank you, Barry. So certainly, thank you again for the opportunity to speak here. I actually had the opportunity last year as well. And I think the point is that I'm getting more and more excited by the data that we're seeing. And certainly, as a urologic oncologist, using a water jet to treat cancer initially was really kind of an absurdity. But the fact that it's a reality today is really, really exciting, and the journey continues to get better and better. So certainly, what I'd like to really go through today and show you and give you some insights into is how we can use the Aquablation system and how safe it can be in terms of cancer control. And again, a lot of the questions that were really asked or I'm asked all the time is, does Aquablation spread cancer? We're using a high-pressure powered waterjet and you're going against the tumor is that going to spread that throughout the body? Can you really use the AquaBeam to get to all parts of the prostate. We know that prostates are varying sizes and shapes, but can you actually use that to get into the peripheral zone, the very outmost reaches of that prostate? Is it, again, does that really truly have that superior safety profile? I think Barry gave you a little insight. It does. But we'll go through some of that. And certainly, does that have any impact, importantly, on the oncologic outcomes? Does it change the cancer progression. And so again, this is very different. Aquablation is not a focal therapy. We've already reviewed and Dr.Gill did an awesome job of that of showing that it is a multifocal disease or many tumors for most patients that exist in the prostate at any given time. And so just going after 1 bit of it really is a failure most of those patients. And ultimately, many of those patients, who receive classic focal therapies will need other radical therapies to get them across that cure line. And so again, we know that when you look at MRIs, they are not -- even though they've moved the bar in terms of our diagnostic capabilities. They're still not perfect and we can't see most tumors, most of these multifocal disease is actually quite invisible. So Aquablation opens that opportunity because it can do a near total resection. We don't really know what to call it, but this is a radical Aquablation, but it's a near total resection of that prostate from the inside out. Starting from the urethra and really going to the very utmost reaches of that prostate. And again, can it access the transition and peripheral zone. The answer is yes, it can get out there. And again, this is very different. There is no other BPH technology even back to open surgery, if you did an open simple prostatectomy, if you're going to go into that peripheral zone, you were doing a radical surgery. So there really -- even the whole lab, all of that can't get to the peripherals zone. But because it's going from the inside out, it has that ability to get there in a safe fashion, it's athermal. Again, we can resect with this more than 95% of all prostate tissue at least that's what we've estimated based on the current experience. And again, it's a near total resection, but it leaves the important parts of the prostate, including that reside right outside intact. Again, it's an athermal type of technology. So we don't have to worry about spread to those nerves. And certainly, at the bladder neck, we're not using the ability to destroy that so we don't have the incontinence rates. And even if the whole [indiscernible], as an example, can do that, you would be causing incontinence in the same mechanism. So again, Aquablation is really positioned in such a unique fashion to treat prostate cancer. And so what we did is throughout the years, and we started our program back in 2018. And so since that time, we have treated many men on active surveillance. Meaning these men had prostate tumors. They were low risk or are there were lower volume, favorable intermediate risk, but they also had concomitant urinary symptoms. And so we wanted to say, well, they needed an outlet procedure because of their urinary symptoms. I really wasn't impressed with our cancer. And historically, I said, we'll just leave them alone, but we're going to use Aquablation because it would help alleviate their urinary symptoms. So what we did was we compared the groups of these. So we looked at men who underwent Aquablation only. So these men, we identified just had urinary symptoms. They did not have cancer. We compared them to our active surveillance group of men, who had also [indiscernible] BPH or urinary symptoms. And we wanted to know, is there a difference in outcomes. #1 is do we improve their urinary symptoms? Are we changing any erectile function or anything with that? And then we also made a comparison because we took that same group of men who had in large prostates and prostate cancer and compared them to a group just on active surveillance and wanted to ask the question of, is this changing their oncologic outcomes? Are we making their cancer worse over time? Are we changing it at all? Or are these men with the Aquablation actually doing better? And so again, here's just a baseline clinical characteristic comparison between all 3 of those groups. Again, Group 1 was a BPH only who underwent Aquablation. Group 2 was the BPH and prostate cancer, who underwent Aquablation. And Group 3 was the active surveillance, only no treatment as well. Again, these are average 70-year-old men. Men on active surveillance alone were slightly younger. The ones who underwent surgery Aquablation had in large prostates, actually most of them were about 100 grams. And they, as expected, those who underwent Aquablation had significantly worse LUTS at baseline urinary symptoms as measured by the IPSS and quality of life scores compared to those, who just are on standard active surveillance. And again, when you look and you say, well, is this safe? Do men who are undergo Aquablation, do we improve their urinary symptoms? It is no surprise that there is no difference, whether they had cancer or not in terms of symptom control. Everyone had significant improvements in the urinary symptoms. Certainly, this is showing out to 6 months. We have the 5-year data on this 5 years. These men are doing excellent and continue to avoid without complaints. If we look at quality of life there, which I'm not showing here -- or I am showing here, they have significant improvements in quality of life. And again, it doesn't make a difference. What criteria you're using, whether you're using PVR, whether you're using MAX urinary flow. Again, these differences and improvements they have after Aquablation are sustained and they have significant improvements. No surprise Aquablation works we've showed this now for years in terms of urinary symptom improvement. The question is, is this safe? So there is a question that patients ask me, there's a question that I get from other physicians. When you're taking this waterjet and blasting away men with tumors is this going to spread? I always then reflect on the fact that I love what I do and I treatment with prostate cancer and the reason why I love this type of tumor is that it is so different than other tumor types. It is what I refer to as the lame, the nice, the snail of tumors. It takes years to develop years to spread. And certainly, I did a lot of basic science research back in the day, where I would actually take prostate cancer cells and try to grow them in mice and stuff. It is very hard to -- even if you take the cells and sprinkle them in mice, it's hard to get them to stick and/or grow. And so certainly, things that we've done over time is we do prostate biopsies over time. We perturb the tumors in these men. It has never been shown the prostate biopsies spread cancer. Certainly, it has never been shown even when you have men with really bad metastatic disease and locally advanced disease causing urinary symptoms that the tumor is so bad in the prostate that these men can pee. We've historically done channel TURPs. Again, no evidence that when we've done a TURP on these patients that there has been any type of spread. In fact, a lot of BPH procedures we do also are unmanned. We don't know, but they have cancer, and there's no evidence that there's enter exacerbation. But we had to ask the question as to say, well, is there a surrogate can we use to say, if we look at circulating tumor cells, is that exacerbated? Are the numbers of these tumor cells that float throughout the blood, are these increased or changed if you do Aquablation? And again, it's a very odd surrogate because circulating tumor cells as an outcome and particularly in prostate cancer actually have very little prognostic value. There are some smaller studies that would suggest that if you do surgery that there you may have a transient increased spike in the circulating tumor cells. I think one study may have implied that it has a higher chance if you have really high numbers that they can associate with the chance of recurrence. But my guess is when you factor in that, it's just the aggressiveness of the overall disease and the overall stage of that patient, that is a higher indicating rather than circulating tumor cells. And so ultimately, I kind of think that this question is a moot point, and we did the initial study as part of the PRCT001 to say, is there a change in circulating tumor cells among men who are undergoing Aquablation? And the answer is, yes, there is a transient spike, what I would call an insignificant increase in the number of circulating tumor cells that happens with Aquablation, it quickly goes back down to a baseline very low number. And I think the point here is I think it's a silly question because there really is no evidence in all of the historic things that we've done to prostate cancer and how we perturbate during surgery or even radiation really has never shown to spread it. So it's not really something that I'm really focused on or worried about. And when we've looked then and said, forget, Brian, what you believe in all that data, what happens to these patients that you've done Aquablation on. So now referring back to those 2 cohorts -- 2 cohorts -- Cohort 2, which is the BPH in prostate cancer as well as Cohort 3, which is active surveillance only. We looked at their cancer outcomes over time. How many of these patients had worst cancers diagnosed that ultimately needed treatment over time. And again, this is a 5-year follow-up. And as you can see here, that top line, the blue line is the Aquablation arm that Cohort 2. And the -- I think it's red arm or purple arm there is the active surveillance only. So in a 5-year period, about half of those patients, who are on active surveillance only were treated with radical therapy, whether that was surgery or radiation. But comparatively, only 20% of men in that Aquablation arm were treated. So again, a significant reduction when you look at a hazard ratio, that's a 58% reduction, if you compare the overall value, that's a 30% difference there. And again, this is a very short-term follow-up. But I also want to emphasize that these men were not treated with the standard protocol that we have developed for cancer control now with AquaBeam. These were generally using the BPH procedures often got into that peripheral zone, but we weren't really intending to treat the cancer. We are really intending to just treat their urinary symptoms. So I think the point here is it is a very safe procedure. And I'm really impressed and actually quite surprised that these men from an oncologic perspective are doing so much better. So then the question is, why not? Again, they have better urinary symptoms. So worst-case scenario, we're improving their urinary symptoms. We have no real change in sexual function. And finally, is if we can change their cancer outcome even if you have low-risk cancer why would we not use Aquablation therapy. Now again, the -- we have to recognize that the AquaBeam is a tool. And sometimes, we get that tool and we develop a protocol and we become so married to using that machine or technology in a certain way. So the BPH, the BPH way, if you will, or the standard way that we use AquaBeam as we do 2 passes with the waterjet. And we create that central defect, which is largely focused in on the transition zone. And we create that hole throughout the prostate, which makes men urinate significantly better. And again, when you look at that defect there, you can clearly see that there's a hole there. This is from the WATER III trial, which was the most recent results released comparing the Aquablation to HoLEP. Again, that defect is very similar, whether you're using the Aquablation or the Holmium Laser to create it. But this is now different. We want to get rid of all of the tissue. So we want to do the Aquablation cancer or the radical Aquablation or the subtotal or whatever we're ultimately going to call it. But I think that anyone in this room can really see, if you look at that far-right picture, this defect is quite impressive. We are getting to the outmost reaches of the prostate to the true capsule. There is very little, if any, tissue that's really left there. So really, really impressive that we can use that tool, but use it in a novel way. So I'm going to next go through how we think differently about using the Aquablation system in this. And again, this is really just emphasizing the fact that traditional Aquablation BPH procedure is really just going after that transition zone and making a big hole in it. But here, we're actually getting way into that peripheral zone. So that question that I get from patients or from other clinicians to say, Brian, can you really get into the peripheral zone? The answer is yes. And again, we use very different passes. And I think that this was the thing that has taken longest to really kind of think about and develop. Again, we become so married to a concept where we're going to use a tool in the same way over and over. But the Aquablation system has so many cool things that you can do. And -- and again, this is now when I do this, I'm not that the normal one was boring, but using now a BPH case is almost kind of run-of-the-mill route. But when you get into the cancer, it is truly becoming a little bit more artistic. Again, the Aquablation system democratizes it. So anyone can do it. But you have the ability to then look at your prostate. And in this case, you can kind of see there that there are 2 yellow dots on the 3D model. Those represent where the cancer locations are that we biopsied or shown up on the MRI and then we come up with subsequent plans. But you can use the Aquablation computerized system and even ultimately, the AI technology to really help you slice and dice that prostate in a really sick way. I just described it, but cut it up into so many different pieces. But ultimately, the goal is all the same, get rid of all of that tissue, and we know we can do that in an athermal and very safe manner. And again, this is really just how we do it is that this is the ultimate image. I look at it and I say, hey, we want to get rid of the anterior tissue as much as we can, and then we want to go after and deep into the periphery we can. And again, the standard BPH procedure uses 2 passes for the cancer cases. We're doing anywhere to 3 to 4, sometimes even 5 or more, just to really cover all of that tissue that we can and use the AquaBeam to its utmost potential. And again, this is just -- the case in particular that we did is that we did that first cut. We went all the way, use that arc as high as we can in our planning to get as much of that interior tissue. Again, our purpose here isn't depth. For this case, we're really just getting transition zone. Remember, again, that most prostate cancer patients are really 40 grams or less. And so this really has an ease of getting all of that peripheral zone. But even on the 130-gram cases, there are ways that you can then subsequently get deep into that prostate tissue. And so we then make 2 additional plans second pass where we are going to depth, and we are going to then maximize to the really peripheral zones. Here is the third path in that same way. Ultimately, we just want to make sure that we clean up. So what we've learned for hemostasis, from the BPH experience was that we used a bipolar cautery or a monopolar cautery device, and we usually do focal bladder neck cautery. And we did that initially because we are saying, "Hey, we want to decrease any risk of any transfusion or significant bleeding." We now use that, but we also use that in navel ways. So we do the focal bladder neck cautery. But then we go and while we're actually using the ultrasound in live imaging, we use that resectoscope, and then clean up any tissue that is there. This additional cleanup is about an additional 15 to 20 minutes. So again, this is not adding significant length onto the procedure, but the average length of this is about a 60-minute procedure versus a 40-minute procedure. But again, when you talk about this in the grand scheme about 1/2 of what it takes or even 1/3 of what it takes to do a radical prostatectomy. So again, when you look at this, I'm so excited because we really have shown that, #1, this is safe. It doesn't spread cancer. Again, all of those skeptics saying that a high-pressure power water jet is going to spread this to people's heads. It doesn't appear to spread, and that is no surprise there. And if you look at circulating tumor cells as a surrogate, it really is no evidence that this is exacerbating cancer. We have reduced Grade Group progression, meaning that these men who receive it, even if you're not doing a full cancer template Aquablation therapy, they're doing better from a cancer control. Awesome to actually see and a very pleasant surprise that even using that, we can actually alter in such positive ways their cancer outcomes. And again, we've evolved it. So now we really are going after all of that tissue and doing a subtotal radical surgery, if you will, to get rid of that and not only eliminate that, but to really hopefully cure them, again, a very different idea. And these patients, I should say, and we're not showing their data really have no difference in terms of urinary symptom control in terms of erectile function et cetera. And it does get to that peripheral zone access because, again, you can use that water jet in so many novel ways. So with that, I am so excited to see how WATER IV goes. And certainly, not to ruin any surprise other surgeons, besides myself have started this journey. And when you look and see that they have easily adapted the techniques that we've developed. So the learning curve on this, even the radical surgery is actually quite low, and it's really cool to have seen these other surgeons start the journey. So thank you, guys.

Thank you, Dr. Helfand, Dr. Gill, Dr. Park. I'm going to wrap-up with some closing statements and then we'll open up with Q&A. But I first just want to commend the 3 of you and everybody else in the WATER IV study, challenging the standard of care in health care and medicine is -- it takes certain breed of surgeon and confidence in what you're doing. Going back to the '90s, I mean, when laparoscopy started, a challenging open surgery. The surgeons were called criminals. Surgeons were called criminals for doing laparoscopy in the '90s. It wasn't that long ago. And now it's like why would you do open surgery if laparoscopy is available. And when you think about just in the 2000s, the introduction of robotic surgery, the challenge to the surgeons to try to advance surgery and saying, what are you doing? And now you think about all the evolutions and what we're doing with Aquablation. And for thought leaders, Dr. -- Dr. Gill is a world-renowned thought leader in the field of robotic prostatectomy. And to sit here and to say we need to do better. There are things -- there's nothing wrong with robotic prostatectomy, but there's an opportunity to improve the care for prostate cancer patients. And to sit here and to say, let's do better is really why we thank you for that. We thank you all the WATER IV investigators because we can do better, and we hope to prove that. So when you think about what we've prided ourselves on a PROCEPT, it's to take on this challenge. We're actually built for this. This is what we do. We don't go do 15 things. We do 1 thing and we do it really, really well. And when we go to the next challenge, the reason why we're standing in front of you and talking to today is we have confidence we're going to do it really, really well. We've built the success of this company on the Level 1 clinical data that we have with BPH. Nobody else did this. How many therapies are out there for BPH? How many have done a randomized study against TURP? We built this company on Level 1 clinical data because we have confidence the technology works. We proved superior safety proved against the gold standard, the efficacy results. And you see the success we've had just over the last 3 years. We just got reimbursement a few years ago. And we've already built the success with the BPH world. We plan to do the same thing now with prostate cancer. When you look at the BPH world, they're just in a few short years. There are over 150 peer-reviewed journals, all in the foundation of the WATER I study, which was that randomized study. That's our goal of prostate cancer. That's why we're starting the WATER IV for prostate cancer study. We're building the Level 1 evidence, doing something nobody has ever done, and we're doing it because we have confidence that we can help patients and we can change the way prostate forever. And ultimately, the goal of WATER IV is to provide men with a frontline treatment option for prostate cancer. It's localized. So thank you, and I'll open up the Q&A.

Craig Bijou, Bank of America. Thank you guys for doing the presentation. I guess I wanted to start with the doctors on the panel. And the reaction to the 001 and 002 data and I guess, your initial reaction there then what do you think the reaction of your peers will be to that data specifically? And I guess the extension of that question is what would be needed beyond 001, 002? Is it WATER IV data that's going to be really needed to convince surgeons about the opportunity in cancer?

I guess I'll start there. Is that -- I think the data from 001 and 002, has really been a dose escalation, right? It's really not a long-term study, and it's really saying it's a feasibility, what do we actually have to do to treat these patients. And so even though I know that the protocol and the intensity or the amount of tissue resection has changed and evolved over time, I'm really impressed with that initial results of saying like, hey, even with what I would now deem as a Monday morning quarterback, going back, I'm like, hey, I don't even know if I did that good of a job initially, but these guys are doing awesome. So if I could do that with a substandard in my opinion, protocol, I'm so excited about what's actually happening when now the full protocol. I think with anything, I think in order to get people to believe you have to have data. I think a lot of companies out there have really gone out and tried to sell you and say this is really going to change up, but they don't have that data. And unfortunately, in prostate cancer, to really get those outcomes, it's a long journey. Because what it really becomes meaningful is not even 5-year, it's 10 years, it's 20 years. And of course, by the time 20 years, we don't know what's going to happen. But along the way, I think we're going to be able to make some pretty convincing statements. What I say is that I used to -- we're at the AUA, obviously. And I used to sit on panels, and I said, it's low-risk cancer, don't touch them. There's no reason, just follow them, et cetera. But now I'm changing the tune and saying, hey, why would you not because there's no harm. Even guys who have minimal urinary symptoms, even those guys improve in terms of their urination. It doesn't cross off any further treatment. So you're not actually saying that, hey, if they would progress over time, you still have those options from radical surgery. It doesn't make it more difficult. It's athermal therapy. So when you operate on those guys if they would progress, it's not like a big [indiscernible] or scar tissue in there to try to remove. So I think when people and other urologists start seeing this, I think the adaptation will be very quick. Everyone and again, it's a biased cohort because everyone signed up to do the study, but everyone who has started using it is now they can't stop. And it's a harder sell to tell patients that, hey, you need the standard of care, radical surgery if you start talking about Aquablation. So I think the patient acceptance will be really easy. I think getting urologists on board will take data, but I think we're prepared and the WATER IV is set up to do that. But I think even just that initial glimpse of 001 and 002, is -- will be pretty convincing to a lot of people right away.

And a lot of the commentary or the comparison is Aquablation versus radical prostatectomy that you guys have talked about. Obviously, radiation therapy is an option kind of in that middle group. So maybe just at a high level, I know there's not data that we have necessarily. But at a high level, just talk about how Aquablation, you kind of see that comparing to maybe radiation therapy and not necessarily the, what I would call, the extreme radical prostatectomy?

Radiation therapy will always have a place. Some folks are just at a genetic level, opposed to having radiation put on their body, specifically for low and intermediate risk disease. I am one of them. I think that radiation, although initially has minimal downside, but when you play it out over 5 years -- 3 to 5 years or further, those are significant. And the problem is that they get worse over time. Radical prostatectomy, you take a hit right away and then everything is healthy and you start healing over time. Radiation is the opposite. Those that do well, do very well. And those that don't -- we don't really have any treatments for tissue that is radiation damaged. So to answer your question, there will always be radiation therapy around. But again, for low and intermediate risk disease where the cancer threat -- the perceived cancer threat is not that huge to have something like radiation put on you is -- many of us feel a step too far, and patients also feel that way.

I'm going to make -- I'm sorry, I'll make a quick comment about reception and urologists or a community group, like I said, we're a 31 urologist. And I announced to our group on Tuesday that we're going to be enrolling patients in WATER IV explained the protocol, was kind of expecting a lot of people saying, why are we doing this? Waterjet does it really make sense? But actually, everyone was receptive. Oh, were there criteria, let's get people signed up because urologists recognize there's this big group of patients with prostate cancer that we don't quite know what to do, meaning, they're nervous. There's something going on. But radical prostatectomy do no harm. We don't want to hurt them, but we do want to help them. And our experience with Aquablation on a BPH level has given a lot of guys in our group confidence that this is something that can be that breached therapy.

Matt O'Brien, Piper Sandler. Thank so much for the clinicians for coming out here today. My apologies. I actually have two questions for Barry. So the first one, Barry, and I don't want to really make too much of this. I just want to make sure that there's nothing we're missing here, but you have more patients at 3 months. We didn't see any 3-month data presented today. Are those patients tracking similar in terms of safety versus the 6-month patients?

Yes. So the reason we anchored the 6 months was to find that comparative data to radical prostatectomy, which typically is not reported at 1 or 3 months where the results are tend to be worse. So we want to kind of do an apples-to-apples. So our data is very consistent, whether it's 1, 3, 6-month data. So that was why we did that.

Got it. Okay. And then a 2-parter here. How are you going to grade group -- or how are you going to measure grade progression in WATER IV, given that I think 95% of the prostates removed. And then is the SHIM score going to be the erectile dysfunction score in WATER IV?

So as far as grade group, it's up to the surgeons on how much tissue is there to biopsy. Obviously, you can do a 12-core systematic biopsy when you have a 60-gram gland, but if you have a 10 gram gland, they're going to have to use their best medical judgment on what they're going to sample. So I think it's going to be -- we're going to have to learn. There's not going to be much to biopsy, and I don't think we've gotten to the stage with this aggressiveness, but they'll biopsy what they can to prove that, that secondary endpoint. Your second question about SHIM, a version of SHIM is being used for the secondary endpoint. It's a particular question in the epic questionnaire, but it tracks very similar. I think I answered all your questions.

Mike Sarcone from Jefferies. Thanks for the presentation today. First one, just for Dr. Park. In your presentation, you had mentioned that you think maybe we can get toward a transition back toward BPH being a surgical-based treatment paradigm. What do you think we need to see for -- to get kind of broad buy-in among the urologist community?

I don't think it's going to take much. I think the -- again, it's about the safety data, the efficacy data and the experience data. And just our small sample size of 31 urologist, again, that quick adoption of 15 patients -- I mean, 15 urologists as we all see what we're doing. I think it's just one of those things you hit that tipping point as more and more do it then everyone wants to jump on board because they get left behind. We have a, I want to say, rival group, but there's another group in talent, and you see that we're blowing up with our BPH practice and they're pushing their hospital hard, hey, we better get this robot otherwise we're going to be behind. And so it really makes me think a lot about Intuitive's of early 2000s, I was part of that whole thing in that arms race. We got the first robot. Who's going to be quicker. And the first is like all the naysayers, is a gimmick. They're just trying to use technology, pony dance, all this kind of stuff. And young people like me where eggs were thrown at us, what are you doing? We have a proven technology, and now you're trying to just begin the key about it. And now here is the standard of care. And I see the exact same parallel with Aquablation. We do have a naysayers. I'm better. I can [indiscernible] prostates. I say, good for you. I'm glad you can run a marathon. I can't. And so these are things that I think that it doesn't take much because urologists, we are one of the most burned-out specialties, and not because we deal with because we deal with a high volume of people. And now we finally have a tool that we can deal with high volumes. And I think once urologists see that, that is to be less stressful and with safe and good outcomes. I just -- I can't -- everyone had that I've introduced I say, hey, come and see it. Everyone just jumps on board. Just super quick, I had, I do his case observations. There was a guy who came in here late yesterday, saw me do 3 cases in the morning. And he was like I said, what brings you here. He's like, well, I'm actually here as a skeptic, I'm not trying to buy one, but I'm young and I want to make sure I tell patients why I'm not doing it. 3 cases later he's like, how do I get one of these things? Seeing is believing. No bleeding. Great huge defects. I'm out of time. I got to catch a plane. I said I don't worry about it. And they're not going to bleed overnight. He goes, you know what, I see it, I get it. I see it. I'm going to do it. I think that's what it's going to take is people seeing it.

Great. And then second one for Dr. Gill. One of the messages we got today is that prostate cancer is the focal. I know CEC also has a HIFU program where you do perform some focal therapy. So I just wanted to get your take at your institution, I'm sure there's some nuance around deciding which treatment to use, but how do you think about using focal therapy versus aquation for prostate cancer?

HIFU is thermal energy. And therefore, if you do whole gland HIFU, you are likely to have sequela. Urethral strictures, bladder neck contractures, difficulty voiding, et cetera, and repeat procedures for taking care of these obstructive issues that result. So that's why at least at USC and at most places, HIFU is restricted only to one lobe, which is fine and dandy, as long as you're talking about GG1 disease. Because the [indiscernible] recurrence in the contralateral lobe is in the 5% to 7% range, that is misdiagnosed or missed cancer on the opposite side, 5% to 7% for GG1 disease. But GG1 disease, let's see whether truly we start doing Aqua for GG1, I'm not sure, okay? We need not do something that doesn't need to be done basically. So we will see how that story evolves. But the bottom line is, GG1 is not the playing ground. And that's not what's going to move all the urologists, okay? It's GG2 and GG3, that's going to get the job done. And I'm sitting here telling you. Sham mentioned, I'm a robotic guy. You want me fired up, I want to take stuff out and do it in the world's best way. I have a hard time looking at patient in the eye today, honestly, when the door is closed, and it's just him and me, I can talk him into anything just by body language rather than actually seeing something. I have a hard time telling these guys, you need surgery. And so to answer your question, HIFU is okay for unilateral, not okay for bilateral. For bilateral, which is what we need to do for GG2 and the low-risk component of GG3. We need to do bilateral. We need to do subtotal, near total. We need an athermal energy, very simple. Cryer won't do it, HIFU won't do it, IRE won't do it, Vapor won't do it. So none of these treatments that are thermal-based are going to be good enough for bilateral clearance. If you're going to do bilateral clearance, you need to come to us, and we'll just do a beautiful robotic prostatectomy. We will bite the bullet, get through the initial incontinence, et cetera, and then get on the other side of that. But if you're going to ablate it bilaterally, then it has to be a thermal and gentler causing no collateral damage beyond the intended. There is always a collateral damage with any thermal energy, cryo or heat is going to hurt the neurovascular bundle sitting right outside. Winters sitting right next to the Apex. And that's why HIFU, for example, we don't even do it if the cancer is within 2 or 3 millimeters of the Apex area. So that is my personal excitement is based on the fact that this is just a new way of thinking about it. And not only just thinking about this treatment -- let's see how the trial goes, but this treatment is going to change the definition of focal. Why do focal unilateral for disease that doesn't need to be treated? And if it does need to be treated, we need bilateral treatment and the thermal stuff goes out of the window. So we have fired up about it as you can tell. And my final comment will be in the few patients that we have already signed up to participate in the trial, it's a really interesting dynamic. And these folks, the primary prerequisite for this entry into the trial is the patient must articulate, I want prostatectomy. The patient comes to us saying, I have decided. I've looked at all the options. I want radical prostatectomy. That is step one. Once that has been articulated by the patient, then we tell him, okay, fine, we get it. What I want to propose to you is a trial where we do either radical prostatectomy right off the bat as you're requesting, or do it in a delayed manner, okay? Let's first do Aquablation and see if we can get into the cancer that way. And if it fails, you will get what you wanted upfront, which is a delayed prostatectomy. Here's hoping we don't need it. And when you start talking about this, then all of a sudden, their mindset goes from what they came in the door with, to now Aquablation then I have to make a U-turn like, okay, no, no, no, hang on. You can't. You can't just say, just do that. The only way you can get it is through the trial et cetera. So as alluded to already, I think patient acceptance is going to be excellent. I think urologists, once they see the -- we're going to nail the 2 co-primary endpoints. The continence and the erectile dysfunction. Those we are going to nail it. No problem. The issue is, are we going to get rid of the entire prostate from the cancer perspective? And as have been shown -- the data have been shown by Dr. Helfand and the team, it is now a different Aquablation. So we have every confidence. And also remember, the FDA has allowed us to do a second Aquablation without penalty. So let's say, for whatever reason, there's a positive biopsy or the PSA dynamics, et cetera, et cetera. We can go to a second one and yet satisfy the FDA. That's the beauty of focal. You can redo it without paying a functional penalty.

Justin Wang with Morgan Stanley. Maybe for Sham or Reza. I was wondering if you can speak a little bit more on the potential for a tools claim for prostate cancer because there seems to be a feeling that this could potentially stimulate some extra aqua utilization in the near term. Also, would you be able to comment on the time line for such a tools claim?

Yes. So regulatory strategy for us is going to be -- it's not complicated, but it's complicated in a sense of we already have an existing product with the FDA, and we're adding indications to it. If you think about the journey that we've gone on our original indication back in December of 2017, we had a BPH indication. We also had a contraindication for known cancer. In August of '23, that contraindication for known prostate cancer has been removed. So we're stepping our way of giving access to men from a regulatory point of view with BPH who are on active surveillance, that's now -- the contraindication has been removed. So the conversations have over the years, have been building with the agency. And so next step is you can't go ask the FDA for anything without data. And so really today, it was the first time that we've stood up here with data. And we need to decide when is the right time to go. When are we going to be most effective with FDA? And probably what's most important is we don't want to do anything that distracts from the focus of enrolling WATER IV. So we wouldn't want to come out and say we could come out with a tool claim tomorrow if we could snap our fingers. But that may start to distract from the interest of being in this study. Then we have layers of reimbursement that we have to deal with. So right now, we're just gathering data, and we're figuring out the best way to navigate with FDA. We're in constant communication with them. But our focus as a company right now is to enroll the WATER IV study because of the importance of that data. Hopefully that kind of helps answer your question.

Ravi Misra from Truist Securities. So just on WATER IV, maybe one for the doctors. Assuming that the data is similar or better to what we've seen so far on 001 and 002, how quickly do you think the WATER IV outcomes can change guidelines. We're talking about 1-year follow-up needed, 2-year follow-up needed? Just kind of how are you guys kind of calibrating that in your heads?

Please correct me, if I'm wrong, that it's a 3-year endpoint?

3 years of follow-up. There is no hard and fast written rule. But I can tell you that 6 months is not enough.

Yes, we are following the patients up to 10 years, but 3 years will suffice. 3 years will suffice as regards the co-primary endpoints, continents and potency. And that is not just based on the 3-month, 3, 6 months, 12 months, but also into -- built into that functional outcomes is the possibility that these patients could fail and go on to radical therapy and have then the incontinence, et cetera, accruing from that. So it is, therefore, per the FDA requirement, they want to have functional outcomes reported at 3 years, in addition to the earlier time points where we will nail it. And because the 3-year endpoint also takes into account oncologic failure that is then being addressed by radical prostatectomy, et cetera. As far as the disease progression, I think the biopsies are built at 1 year and 3 years and that should give us the necessary oncologic confidence.

Barry, can you maybe just clarify guidelines versus label for [indiscernible]. That would be helpful.

So this is an evolution as with anything. So first step is you have to have regulatory approval. Our regulatory submission will be based on our co-primary endpoints, which is at 6 months. So that will start the engagement with FDA to have something on label. Then you get into the world of reimbursement coverage and the world of guidelines. And those could take months to years later. But really, as a company, our first green light that gets handed off to Sham is the day we get FDA approval, which starts from this co-primary endpoints. Now the reason we're gathering 10-year data is ultimately for adoption. Some people are good with 1-year data. Some people want to wait for 3-year data, some people want to say 7-year data or 10-year data. And so that adoption curve, that's why we're running such a large studies. Sham, if you want to add anything to that journey of accomplishments.

The only clarification in the sense of in the sense of the reimbursement is we have established reimbursement now. We have to make a decision as a company with prostate cancer, whether we want to try to get more reimbursement for prostate cancer. So we have fantastic reimbursement, the levels that we have today for the BPH procedure are sufficient for a prostate cancer procedure. So we may have an opportunity due to the techniques that Dr. Helfand showed, the different technologies that are used in cancer maybe go after additional reimbursement as well.

Great. And then just maybe one more. It was really interesting. I thought when you kind of laid out installed base evolution between 1Q '23 and 1Q '25. Just curious, as you're kind of going more into that low and medium volume opportunity now. Can you talk about how long it takes one of those centers to kind of come up to a high-volume center? And then kind of are you indifferent to kind of going forward, where you place systems because you have visibility into low-volume hospital becoming a high-volume hospital.

It's typically well within a year that we see that volume get up to a high-volume hospital. It takes 3-6 months for a new surgeon to kind of start getting going. And then by the time the year comes up, you have multiple surgeons using the technology. And I mean they're still growing. But at that point, take surpassed this level of no longer being a low or medium volume hospital. So within a year, it's still a good time frame it takes to get these hospitals up and going. As far as the strategy or the placement, we still have so much opportunity with high-volume hospitals continues to be the kind of the North Star of where we're going. But surgeons driving and not only that, but hospitals are now beginning to part of that conversation. So when talk about the strategic idea and our focus and our time we spend with them, it's not that we weren't selling to IDNs for the last 3 years. We've had a lot of success selling to the best IDNs. What's changed in 2025 is they are bringing us into the conversation now. They're inviting us to the table to say, let's look at the next year, look at next 3 years. Here are all the opportunity. Here's the data, and we provide them the data. We show them, here's where you're losing patients. Here's where the patients are going. And so what they want to do is bring those patients back, bring those surgeons back to their hospitals. So they may say this is a hospital we believe it could have a high-volume BPH program. If we can get the surgeon to come over here, then we want to invest in Aquablation. So we have to still the surgeons excited. Surgeons have to go watch Dr. Park. They got to believe in it. At the end of the day, the hospitals are going buy -- they're going to buy robots for surgeons that utilize them. And ultimately, we have success in that business plan. So the strategy is still the same, drive Aquablation procedures, whether it's a low volume hospital or high volume hospital, we still have success there. So it's about surgeons really wanting to drive the growth of the technology.

This is Mike Kratky from Leerink. Thanks for the thoughtful presentation. Maybe one for Dr. Park. Looked like TURP volumes at your center have come down a lot between 2021 and 2024, but still represents a decent chunk of volumes overall. So can you talk about what dynamics are keeping certain physicians or procedures being done on TURP today? And what needs to happen for that to switch to Aquablation at a higher rate?

Sure. So we're 31 urologists, covering Kansas City area. So we cover probably -- I don't know exactly maybe about 8 or 10 hospitals. Currently 3 hospitals have them, and so it's really an access issue. So every hospital that has Aquablation at all those hospitals, doctors have converted to Aquablation. So I would say those TURPs are all done have places that don't offer it or don't have it. And so I just see it as time goes on, and that was 1 the questions we asked as a group strategically, do we try to just -- because we have to partner with hospitals to -- for this. And the question was like, what hospitals we partner with as we started using it, we thought we had to be strategic, but honestly, every hospital that has TURPs is using Aquablation. So that's our strategy now because where you treat BPH with Aquablation because that's really going to become the standard of care.

Understood. And maybe for the physicians on the panel, just going back to the prostate cancer side, you've had a few questions on kind of the regulatory approval versus the guidelines. In terms of the WATER IV data specifically, do you think that, that 6-month data on incontinence and erectile dysfunction is going to be sufficient to drive adoption among your colleagues on the prostate cancer side? Or do you think it's going to be GG progression? What specifically in the data do you think is really going to drive the commercial front?

It's going to have to be cancer control. I think that we are already anticipating and expecting and all signs indicate that the continence your erectile function is going to be preserved. It's really the grade group progression saying, hey, if we can alter the natural history in a way that only helps patients in terms of urinary control doesn't have to provide really any risk of harm. That's the necessary piece. And so whether that's a year data or a 3-year, I think any change is going to be a signal that to proceed. But I think they're going want to see that.

Brandon Vazquez from William Blair. First one for Dr. Helfand. Maybe I can ask you your question, you had asked this, why not? You now have this great data in your own practice. You know what it's like to leave patients on active surveillance. When you go home Monday and you see your patience, why are you going to continue to put them on active surveillance given what we know today?

Well, they're still on active surveillance. So again, they ultimately, because we don't know all of the patients that are treated are put back on it. But I was actually telling very last night I go, you guys have kind of ruined my practice. I used to do only really robotic prostatectomies, And really, this has changed it. And the number of patients that are coming and specifically seeking care, whether on a trial or they have urinary symptoms and have cancer and saying, hey, I just -- it's extremely high. So it is a harder discussion for me, and it's more now insurance coverage more than anything else of saying like, why not, because as soon as patients are hearing about this, again, remember that first cancer diagnosis, they're saying, hey, I have cancer and you are talking to them off a ledger saying, no this is low risk. You're fine. This is not spreading. But usually, there's spouse or other ones saying that you should be treated. This is cancer, and so it's talking people off the ledge. This actually represents a nice alternative to say, hey, we're influencing the best we can tell your cancer outcomes. But whether it's going to last in the long term, we don't know. But certainly, in the short term, it's having positive results. So again, I'm biased in the experience and my response here. But if I could, I have a skeptic sitting next to me and saying like, hey, I don't know we're going to -- we want that data. But in that short anecdotal experience, I am almost ready to say, hey, every patient diagnosed with low risk or intermediate risk, we should at least have this conversation.

Maybe a follow-up for the PROCEPT team. Two questions, and I'll throw in together here real quick. The first, Kevin, on the call yesterday, it sounded a little bit like you were alluding to maybe discussing enrollment time for WATER IV today. Maybe I was over reading that. But given the excitement we're seeing here when you explain this to patients, any thoughts on the latest enrollment time lines? And then just overall for the whole PROCEPT team, you know the mechanism of action. You guys have data confirming a lot of this. You have enthusiastic KOLs here. What keeps you up at night when you think about going into the cancer market over time?

So we've instructed people to not talk about the time line, so maybe I'll do that on the panel's behalf here. I think given the trade-offs that Dr. Helfand described, I hope everyone appreciates why it takes time to enroll a trial like we're doing here. So we have a few goals internally. By the end of this year, 12 months we would like to roll the majority of patients, so greater than 50%. We think a very realistic time line for enrollment would be full enrollment at 24 months. I think that would be a very reasonable goal and a very reasonable type of time line. With that said, we do think we could perhaps get it done somewhere in that 18 month range. And I think expectation should be 24 realistic. I think aggressive is 18 with the majority of patients enrolled within 12.

As for the second part of your question, I mean, definitely, we have to make sure this trial is to manage according to the protocol, and we are very excited about it. But we don't want to lose the site of our opportunity in BPH as a company. Definitely prostate cancer. We are very excited about. As I mentioned, we are on pace to be #2 receptive procedure and our goal is to close the gap and be the leader in treatment of BPH, the surgical treatment of choice. So we have to keep an eye on that. So as we are doing cancer, I mean, we are definitely very excited about our opportunity in BPH.

I'll actually answer the cancer side. I wouldn't say what keeps me up at night, but we still have a lot of questions that need to be answered. I mean the reality is, is there's a lot of urologists that do bread and butter BPH surgery. The specialty of prostate cancer has got consolidated over the years. And so how do we ensure that our prostate cancer surgeons who don't do BPH, become educated and proficient in Aquablation as quickly as possible in the coming years, will be something we'll tackle. So it's something we need to address today. But it is something that we will have to take on. And as Dr. Helfand can speak to, and I think the learning curve is something that can easily be achieved. It's just more of a strategy and question how quickly we move on educating the prostate cancer community to Dr. Gills of the world and getting them on board with Aquablation. I don't know if you are going to des that, but that's something that we'll have to take on in the future. I think we did our closing. Thank you.

Thank you for attending this Investor Day. Thank you to the physicians and surgeons for sharing your perspective, Barry and Sham. And I hope to see you -- have a great conference and see you in the future meetings.