Good morning, everyone. I'm delighted that you have joined us today. Friday, March 13th is a wonderful day. As you know, TULSA-PRO is a treatment modality for prostate disease, and although it is a device, it is important to develop the clinical data to demonstrate the clinical value of the technology or adoption. While we are a medical device company, we behave more like a biotech company in that regard, and we invested about $20 million to sponsor the most comprehensive Level I trial that has ever been done in the prostate cancer space. The results of the trial are beginning to be published and will read out for the next 10 years. Today, I'm delighted that Dr. Klotz is with us to present the first six months of the outcomes data. Before I turn it over to him, here's our standard forward-looking statement. Dr.
Klotz, one of the most renowned urologists in the world, take it away, please.
Thanks, Arun. Give me just a moment. Let's see now. Advance screen. Okay, thanks. Morning, everyone. I'm here in London, the U.K., at the annual meeting of the European Association of Urology. This is now the largest annual urology meeting in the world. I think about 15,000 attendees. I just actually presented this data this afternoon in the late-breaking abstract session, which is a very high-profile session. It's definitely the importance and uniqueness of this trial has been recognized now quite widely. The need for change. The TULSA is directed at patients with intermediate risk prostate cancer. That's also called Grade Group 2 to three out of five. This is very common. Probably about half of newly diagnosed patients fall into this group.
There is an unmet need for a treatment for these patients that is oncologically effective at eradicating the cancer, but also preserves quality of life. Existing definitive therapies, primarily surgery and radiation, both carry with them significant risks. For patients with higher grade cancer, those risks are worthwhile. Intermediate risk patients tend to have a fairly slow-growing disease. Untreated, many of these patients are not destined to die of the disease. There is a very significant unmet need for an effective treatment that will reduce the risk of metastasis and not interfere with voiding, with continence, with erectile function. The unique thing about TULSA is the precision, and the precision is a function of MR thermometry. MR can provide a real-time thermal map of tissue.
In a normal person, that would be very uninteresting because everything would be 37.5 degrees Celsius. If you're using thermal energy to treat tissue with the goal of eradicating cancer or inducing reduction in volume of the tissue, the temperature that you achieve becomes critically important. Existing ablation methods, of which there are several that are trying to achieve the same goal of quality of life preservation and effective treatment of the cancer, lack the precision that characterizes TULSA. If it's a treatment called HIFU, it's very relatively inaccurate. The result is that you have to deliver a lot more energy than is actually required, and that results in further side effects. We live in the era of evidence-based medicine.
We have very good phase II data, non-comparative data for both effectiveness and safety of TULSA called the TACT trial. I'll show a little bit of data about that. To change practice, you really need comparative randomized trials to make new technologies part of the standard of care. This, I think, audacious trial, the CAPTAIN trial, which I'm gonna show you in a moment, is an attempt to do that. There's been many people have tried to do randomized trials comparing radical prostatectomy, which is quite a major operation, to a less invasive treatment. Almost always these trials have failed because patients were just unwilling to undergo that kind of randomization. This trial, which now has accrued successfully, is really a major historic achievement, I would say.
This is just a brief summary of TULSA. I'm not gonna go into detail, but it's the full name is MRI-Guided Transurethral Ultrasound Ablation of the prostate. It's ultrasound energy that is converted to heat in tissue. The device goes into the urethra. It's the size of a typical male sound that urologists use all the time, goes quite easily, and it has these 10 5 mm transducers along the more distal part of it that sits in the prostate. Each one of these is individually controlled, corresponds to a 5 mm MRI slice. Previous studies, including animal studies, treat and resect studies where we treated the patient with TULSA and then went to the operating room and took out the prostate, showed that the precision of this technology is within about 1-1.3 mm.
It's safe. Unlike HIFU, for example, no energy is going through the rectum, and therefore the rectum is not at risk of injury, which can be a real potential problem. Some of the other features are a Thermal Boost, which allows you to drive the heating a little bit beyond the normal boundary, which is about 3 cm from the urethra, the radius of that distance there. Contouring assistance, which incorporates artificial intelligence to enhance the accuracy and the speed and efficiency of outlining the target. So that's essentially the background. Just a minute or two about the journey to get here. This goes back almost 20 years, beginning with in silico and gels, and then a several-year period of experiments, mainly canine models, dogs, where the treatment was administered to the dog and then the prostate removed.
This essentially showed, as I mentioned, correlation between the area that was targeted and the area that actually was treated of 1.3 mm, which is pretty remarkable. Then this led to treat-and-resect studies in humans. Same idea. This was done by me, where we administered TULSA. In those days, it took around 5 hours on average. It's much quicker now. Then took the patient up to the operating room and removed the prostate. The first few cases, frankly, I wasn't sure if this was gonna be like resecting jello. What was the consistency of the prostate gonna be? But it had cooled off, and it was fairly normal type of operation from my perspective. It again showed this accuracy.
This led to this large scale trial called the TACT trial, 115 patients, the so-called pivotal registration trial. What this showed, first of all, the safety that the patients had almost no rate of incontinence that was durable, that erectile function recovered to around 90% of baseline by six months after the procedure, and that the procedure was effective. 80% of patients at five years had their disease controlled by TULSA alone. I should also emphasize that this was early days, so there was a real learning curve phenomenon, not only in terms of the individual sites becoming more comfortable with the technology, but even more so, all practitioners learning from that experience which patients did not do well with TULSA.
We're much better now at patient selection, and I'll go into some details about that in a moment. This was tremendously encouraging. An effective therapy preserves quality of life. 80% success is very comparable to just about every other treatment, including radiation and surgery, in terms of the likelihood of patients re-requiring subsequent therapy. Five years with prostate cancer is too soon to see mortality endpoints. It takes longer than that for a localized disease to become lethal. Disease control is really how one evaluates effectiveness. This is a presentation from the EAU, which was just given by me about an hour and a half ago. I'm on advisory board and a consultant, receive research funding from Profound, but I have no equity in the company.
This graphic kind of shows the ten slices, the patient in the MR core under general anesthesia, the urethral applicator, which is a relatively small, rigid device that any urologist can put easily into the urethra with the ten 5 millimeter slices sitting along the prostate. The maximal length is 5 cm. That is greater than the length of about 97% of patients' prostates. As I mentioned, you can treat out to a little over 3 cm from the urethra, which also encompasses all but the very largest prostates. There are ways to drive the energy out even further. Here's the trial design. Pardon me. This was 211 patients that were randomized two to one to TULSA versus radical prostatectomy. In other words, of every three patients, two got TULSA, one got surgery.
There were several reasons for this 2-to-1 randomization, but the main one was to make the trial more appealing to patients. This was primarily offered to patients who were heading towards surgery, and when you give them an option of a non-surgical treatment, they grasp at it like a drowning man grasping at a straw. Patients are not eager to have radical prostatectomy these days. Why that is another story. I will just say that it was quite rapid accrual and a very low proportion of patients who actually got randomized to surgery and then bailed out. That was a concern. In fact, it was quite a small number. There were almost no patients randomized to TULSA who elected to cross over and have surgery.
The eligibility criteria, as I mentioned, was intermediate risk, so-called Grade 2 or 3, PSA less than 20. Sorry. They had to be good TULSA candidates. The main exclusion criteria were if the distance to the lateral aspect of the cancer was more than 3 cm or if they had a large calcification. Calcifications scatter the ultrasound energy. You can't get good heating beyond that point, and so if there's a cancer there, that's potentially a deal breaker. There were two co-primary endpoints, safety and the oncologic endpoint. The safety endpoint is going to be assessed at 1 year, so the data I'm presenting here is earlier than that. The oncologic endpoint is gonna be assessed formally at three years, and these are kind of typical oncology endpoints, PSA, MRI findings, biopsy. Everyone in the TULSA arm got biopsy.
Obviously, once the prostate's taken out, usually there's nothing to biopsy, and the need for secondary treatment, and there's a whole slew of other secondary outcomes. This was a major undertaking. There were 15 sites from four different countries, 22 investigators. Most of these investigators are well-known names in the prostate cancer field. Also importantly, these are sites with acknowledged expertise in radical prostatectomy. In fact, we have a number of metrics showing that the quality of the radical prostatectomy was very high. Randomization is done to reduce bias and imbalance due to known and unknown confounders, and that in fact worked very well in this study.
You can see these are risk factors that if there was an imbalance, could influence the outcome, and there was no imbalance in any of them, PSA, prostate volume, whether they were Grade 2 or 3. The clinical T stage, this has to do with whether there's a palpable lesion or not, and baseline erectile function and continence. Essentially, no significant difference in any of them. This is an example of one of these cases. You see here, this is subtotal ablation, treating about 75% of the prostate. It was a posterior lesion at the back part of the prostate. You can see that the right side anteriorly is not being treated. That, in fact, is a place where prostate cancer is normally not identified. In the absence of any imaging or biopsy showing a lesion there, it's considered quite safe to leave that.
Since this was being compared to radical prostatectomy, which is whole gland, most of the patients, about two-thirds, got the whole prostate treated. About a third, it was this type of subtotal ablation. The surgery, almost all patients had a nerve-sparing operation, completely appropriate. You're looking at preservation of erectile function, and about three-quarters had a pelvic lymph node dissection done concurrently. This is consistent with the standard of care. What you see here in these three sets of images are the initial targeting that's done now with artificial intelligence assistance. Makes it a lot quicker and more accurate. The actual treatment, and then the bottom is the post-treatment contrast study. All you're seeing basically where the prostate was is a big black area. There's no perfusion at all. It's been destroyed. Here are the results.
This is first perioperative result. You can see, not surprising, essentially no blood loss with TULSA. You're putting this applicator in through a normal orifice. It doesn't bleed. On average, with the surgery, only 150 cc's of blood loss. That's extremely good as an average and suggests that it's a quality assurance measure that the guys doing this operation knew what they were doing. Length of stay, TULSA's an outpatient procedure. One or two patients stayed overnight, but by and large, they go home the same day. With surgery, again, quite favorable. Average 1.1 days in hospital, but which is pretty good, but still longer than with TULSA. Over on the right, you see the pain score, and again, no surprise, the patients have very little pain after TULSA.
My experience is patients wake up afterwards and say, "When are you starting the procedure?" They're not even aware they had it. With surgery, for a week or 10 days, you get quite a bit of pain. This is a modest but real advantage of TULSA that there's considerably less pain the first week and a half or so. This is overall health out to day 30. This is basically asking the patient, you know, "How are you?" and trying to rate it on a visual scale. No surprise, surgery, even robotic surgery, causes a decrease in overall health, which lasts, gradually improves out to about a month, sometimes longer. It's interesting with TULSA that there's a slight drop, but by about three weeks afterwards, the patient's quality of life actually was above baseline.
I think the best explanation is relief that they were diagnosed with cancer. Now it's gone. That improves their overall sense of their overall health. It certainly returned to baseline quicker than with surgery and even at a higher level. Now we're getting down to really some of the nuts and bolts of this, days off work. The average was 10 with TULSA. It was 19, almost twice as long with surgery, with a much greater interquartile range. Some patients off as long as six weeks. Again, this is consistent with clinical practice. About 6% of patients had to be rehospitalized after surgery. There was only a single patient hospitalized after TULSA. I believe it was a urinary tract infection.
Patient made a rapid recovery, and a couple of patients after surgery got really sick and required ICU admission, none of them after TULSA. Fewer admissions to hospital, fewer serious complications, less time off work. This, I would say, is the most important data from the trial that we have so far. This is recovery of continence. Around 80% are continent by six months afterwards. We expect that's gonna improve further. The data from the earlier TACT trial was about 90+% by a year. With radical prostatectomy, you still had half of patients roughly with incontinence at six months. This is consistent with patient-reported outcomes from other radical prostatectomy trials. There's a controversy in the field about how common incontinence is after surgery.
I think most surgeons who are honest about this acknowledge that a relatively high proportion of patients have persistent and prolonged incontinence, mild in most cases, but still it's there. As far as erectile function, again, more rapid recovery with TULSA than surgery. This is the composite endpoint, the likelihood that the patient has both continence and erectile function, and it was twice as high with TULSA compared to surgery at six months. This will evolve. You know, it's gonna look probably better by a year, but still, TULSA certainly outperformed surgery in terms of recovery, functional recovery at six months. This is the only actual oncologic or cancer-related outcome we have at this point, which is the surgical pathology. You can see that about a third of patients had extracapsular extension. pT3a means microscopic extension.
pT3b means gross, extensive resection outside the capsule, through or outside the capsule. More importantly, a third of the patients had positive surgical margins. Now, that is consistent with other results for a patient cohort like this, intermediate risk. It's certainly not low. It does have significance in terms of the likelihood of PSA recurrence. Not all these patients are gonna recur. Some patients with negative margins can have a PSA recurrence. Time will tell. Again, it's that we're gonna have some of that data in another six months. But I think it's partly a quality assurance issue that these results are consistent with many other series of radical prostatectomies. That's the data. This is a historic trial.
It's really the first time that you had a large-scale multi-center trial comparing surgery to an energy-based intervention that accrued successfully. Contamination rate, meaning the number of patients who switched treatments from what they were allocated to was quite small in the range of what was anticipated. At this point, TULSA outperforms surgery in terms of safety and functional recovery. And all these secondary endpoints, blood loss, length of stay, return to work, et cetera, TULSA looked better. Now, of course, the $64,000 question is cancer efficacy. We don't have that yet. It's coming. We'll have the first signal in about six months, which will be the PSA recurrence rate after surgery and the biopsy results. All patients in the TULSA arm had a mandated MRI and biopsy at one year, so that data will be of huge interest. Stay tuned.
Thank you very much. Let's see now. Here. Stop share. There we go. Thank you.
Okay. Thank you, Dr. Klotz, for that impactful presentation and for walking us through the CAPTAIN six-month outcomes. What I'd like to do now is step back for a few minutes and place CAPTAIN in the context of the total body of evidence supporting TULSA and explain how this positions us for continued progress towards inclusion in prostate cancer professional society guidelines. While Dr. Klotz focused on the CAPTAIN results, those outcomes sit on top of a solid clinical foundation. Today, TULSA is supported by more than 70 peer-reviewed publications and over 200 scientific conference presentations. This evidence spans the full clinical spectrum from gold standard treatment effect studies that establish precision through to the TACT FDA registration trial and into extensive real-world experience across multiple disease states and treatment strategies. Importantly, this body of evidence wasn't built in a single way or for a single use case.
We've supported both sponsored and investigator-initiated trials to demonstrate that TULSA is not only effective but flexible and customizable across whole gland treatment, partial gland treatment, large prostates, salvage settings, combinations of cancer and BPH, and patients with BPH alone. Our open International CARE Registry captures the spectrum as any patient treated with TULSA, regardless of disease state, is eligible to be included. The takeaway is simple. TULSA isn't a niche solution. It's a platform that can be applied in many different ways while delivering consistent, predictable, and durable outcomes. One of the most important things the community looks for is consistency, and that's exactly what we see here. Consistency across multiple studies, which supports predictable and durable outcomes. The graphs on the left show long-term functional recovery from the TACT FDA registration study tracked out to five years.
The graph on the top left is preservation of urinary incontinence, and the graph on the bottom left is preservation of erectile function. At six months, pad-free urinary incontinence was 86% and erectile function sufficient for penetration was 56%. What's important is what happens next. Both measures continue to improve beyond six months and remain durable over time, with continence rising to about 92%-97% and erectile function continuing to recover through 12 months and beyond to 76%-87%. On the right, I'm showing the same graph Dr. Klotz presented with the six-month CAPTAIN outcomes. TULSA is in dark blue and robotic prostatectomy in orange. What I've added is the light blue, and that's the corresponding six-month data from the TACT study. You can see visually how well the TULSA data sets from CAPTAIN match those from TACT at the same time point.
The message here isn't about a single number. It's about predictability. When outcomes repeat across independent studies, different sites, and different patient populations, not only does that speak to the technology itself, but that also gives us confidence that what we're seeing in CAPTAIN will continue to track positively over time. These favorable outcomes are not accidental. They're a direct result of how TULSA works. As Dr. Klotz described with the various sets of images, here we're showing a representative case of whole gland ablation of a patient with intermediate-risk bilateral prostate cancer with a prostate volume of 44 cc's ablated completely in 38 minutes. The top row of images shows what the surgeon sees during treatment planning. Using high-resolution in-bore MRI, the prostate is defined precisely.
Today, AI-based contouring, which was demonstrated to be equivalent to those from expert radiologists, automatically appears on the screen and helps the surgeon makes faster planning more consistent and highly accurate. Also of note is the fact that these treatment plans are based on live in-bore MRI, meaning that surgeons are not using old diagnostic MR images that they have to register to a live ultrasound image. Anecdotally, we are hearing from our users that in about 30% of cases, they're defining a different treatment plan than they would have if using older MRI registered to ultrasound. That means that the live in-bore image is showing cancer extent more precisely and confidently than older images layered with non-trivial registration errors. During treatment, the surgeon sees live MRI thermometry, shown in the second row of images. This is critical.
It allows closed-loop real-time control of the ultrasound energy, heating tissue pixel by pixel and degree by degree, while allowing the surgeon to visualize exactly what is being treated and what is being spared. Here we see gentle ablation to 57 degrees Celsius, which kills the tissue but doesn't boil or char it. TULSA achieves this treatment effect using less energy than other ablation devices, which is a key factor in why TULSA patients recover quickly and experience such a positive perioperative result and functional integrity. Immediately after treatment, the bottom row of images shows contrast-enhanced MRI, which confirms the non-enhancing, non-viable dead tissue. That confirmation step gives surgeons confidence that the intended treatment was delivered exactly as planned. This combination of precision, flexibility, and real-time feedback is what underpins the quality and durability of TULSA outcomes. TULSA gives surgeons an extraordinary level of flexibility.
They can design truly customized treatments based on individual anatomy and pathology, whether that means preserving urinary continence, erectile function, or even so precisely that they can carve out the ejaculatory ducts, all the while still fully treating the cancer. In the real world, surgeons can use this flexibility, which is not always the case in more strict clinical trial settings. This level of customization applies across prostate sizes and disease indications from focal lesions to bilateral disease and to very large prostate glands. TULSA allows surgeons to tailor treatment in ways that simply aren't possible with other modalities. This provides TULSA a large addressable market and provides surgeons a tool they can use efficiently across their practice. One finding from the TACT study surprised even us. At 12 months, an independent central radiology lab measured a 92% reduction in prostate volume following TULSA. That tells us two important things.
First, it demonstrates durability. If the prostate tissue is gone, there's nothing left to harbor cancer or support regrowth. Second, we ended up measuring that this degree of volume reduction translates into meaningful symptom relief for men with lower urinary tract symptoms or LUTS due to BPH. I'll leave that thread intentionally open because Arun will speak next about how we started in cancer and are now expanding into the BPH space. This slide summarizes how we built the TULSA evidence base deliberately and correctly to support adoption and guideline inclusion. We started with treat-and-resect studies, which are foundational gold standard science. They prove beyond doubt the precision of the technology. Next came TACT, a Level IIb pivotal trial used for FDA clearance, providing durable five-year safety, quality of life, and oncologic control data. In prostate cancer, five-year durability is essential to be taken seriously.
We added real-world studies, also Level IIb, which show how TULSA performs in everyday clinical practice with customized treatment plans. These studies best reflect the outcomes patients can realistically expect. For example, some of our real-world studies demonstrate 100% preservation of urinary incontinence and 84% preservation of erectile function. We followed that with high-quality systematic reviews, Level IIa evidence, which supported our achievement of CPT Category I codes that took effect in 2025. Now with CAPTAIN, we have Level I evidence. This is critically important because CAPTAIN enables direct head-to-head comparative analysis. That allows definitive conclusions, the kind required for recommendation statements in professional society and clinical practice guidelines. One important distinction, absolute patient outcomes are best understood through real-world data, while CAPTAIN validates comparative performance. Together, they complete the picture.
This is my last slide, but I wanted to take a couple of minutes to explain what the CAPTAIN data release really means, especially in the context of clinical guidelines and why this is best understood as a process rather than a binary outcome. There's often an assumption that a Level I trial either gets you into guidelines or it doesn't. That's not how professional society guidelines actually work. Organizations like NCCN, AUA, and EAU are deliberately conservative. They move based on the totality of evidence that builds over time, not on any single study. In practice, new technologies tend to follow a predictable path. They start out as experimental, then the modality's recognized conceptually, but not named. Over time, the technology is explicitly mentioned, often with restrictions like use in a clinical trial or registry.
From there, it becomes recommended for a defined subset of patients and eventually reaches full guideline inclusion. That's how innovation gets absorbed into clinical practice. You can see this clearly with TULSA in the NCCN prostate cancer guidelines. For years, NCCN discussed ablation without naming specific technologies. In the 2025 update, TULSA was mentioned by name for the first time, and the guidelines clearly distinguished focal and whole gland prostate ablation. That's a meaningful step forward. At the same time, it's still classified as experimental with the recommendation that treatment be done under a clinical trial or registry. That aligns directly with how we operate today through our International CARE Registry. CARE isn't just about data collection, it's structured to fit within current guideline language. Because of that, we've already seen insurance companies approve coverage when patients are treated under CARE.
Guidelines are not blocking access. They're evolving alongside the evidence. This is where CAPTAIN matters. CAPTAIN is a Level I trial that materially strengthens the evidence across safety, oncologic outcomes, functional results, and consistency. It doesn't flip a switch overnight, but it moves TULSA along the guideline continuum towards defined recommendations for appropriate patient subsets. The key point is that this no longer is about whether TULSA belongs in guidelines. The modality is recognized, the technology is named, registry-based use is guideline consistent, payers are engaging. From here, it's a matter of time and evidence maturation. This matters commercially because our biggest challenge today is awareness. Many patients are never told that TULSA exists as an option. Once a therapy is embedded in guidelines, physicians are obligated to present it as an option, whether or not their hospital even offers it.
That change fundamentally alters awareness and adoption. CAPTAIN isn't the beginning or the end of the story. It's a critical inflection point in a well-understood guideline evolution, and we're moving along that path with momentum. With that context, I'll now hand it over to Arun Menawat, our CEO, to discuss what this growing body of evidence, including the CAPTAIN results, means for our business and future growth.
Thank you, Mathieu. All good?
The number one thing that we hear from patients is that TULSA-PRO was never actually offered as an option to them. As Mathieu mentioned, that once this clinical data is published and out with all of the oncological outcomes as well, that it will become effectively based upon guidance from the hospitals themselves, it'll become nearly a requirement to be able to present this as an option, or TULSA-PRO as an option. We're pretty excited that this is being presented. I'm having difficulty with the screen here. Give me one second. That's the first thing that I think, as Mathieu's already talked about.
The second thing is that when we talk to physicians, the number one thing that they talk about is that they are looking for a modality that can be used in a wide variety of patients. I think that based upon the data that Dr. Klotz presented and the data that Mathieu presented, I think TULSA-PRO is one of those modalities that allows us to be able to create what we call TULSA-PRO days, and this allows the flexibility in scheduling the patients as we go forward, as well. The idea being that they can schedule a full day of TULSA-PRO patients. They're able to use it on a whole gland treatment, they can use it on a focal gland treatment.
They can also use now in patients who have symptoms of BPH, because we have just introduced a new software, which is also AI-based, that allows the same technology to be able to provide a partial ablations that are targeted for what causes the BPH to be able to treat in a competitive timeframe. That's the most important thing. It can treat in the most competitive timeframe. The idea is that technologies get adopted that are used in a wide variety, but also have the phenomenal clinical evidence that we have developed. The last thing that I wanted to mention is that, you know, in the last analyst call, I explicitly talked about the value that MRI brings to TULSA-PRO. As Dr.
Klotz mentioned, it's about the precision, it's about the ability to visualize all the vital organs, anatomy, to be able to avoid, you know, killing the parts that need to stay, keep, and the parts that have cancer is generally visible and are able to incorporate that sections. So far, you know, we've been using MRs in existing hospitals with existing MRs and that has, you know, that is coming along. Over time, over the last few years, in parallel, MR companies have also recognized the future of MR in the interventional space. As a result, as you already know and that we have talked about, Siemens already has an MR, an interventional MR that is now beginning to get marketed for interventional purposes only.
To us, this is about the future of surgery. It is MR image-guided, it is TULSA-PRO-type technologies for a variety of disease. The first showcase of this new future of surgery will be presented at the Society of Interventional Radiology, happens to be in Toronto this year. It starts on April 11th. The exhibits are from April 11th to April 15th. For those of you who are interested, I invite you to really come visit the conference at the booths, and you will hopefully be able to see the future of surgery. With that, I would, you know, these are all the prepared remarks. I would invite you to, you know, if you have any questions, to raise your digital hands.
Stephen Kilmer will be able to see your hands and write your comments, and he will be able to then ask the questions. The whole senior team is here, and we're very happy to address your questions.
Arun, there's a few questions in the chat, which I can address if.
Yeah.
Fantastic.
Dr. A, I'm just gonna read those out loud when we get to those, and then you can address them, if that's okay. 'Cause the rest of the group can't. The participants can't see those questions online.
Yes. Okay.
Thank you. The first question is actually coming from Michael Freeman, an analyst at Raymond James.
Do you want me to read it?
No, Michael, it's your line should be open. You just have to
Yes. Can you hear me?
We can
Yep.
Thank you.
Fabulous. Okay. Well, first of all, congratulations on these positive data and just getting the CAPTAIN trial done. This is a big feat. My first question, I'm just gonna dig into the data a little bit. Looking at the rates of erectile function, you know, they appear relatively close to robotic surgery at six months. Would you have expected greater separation here? If so, what would you attribute these relatively close outcomes to?
Actually, there was another question about positive margin rate being high, and I think they're related. You know, when you do studies like this, multi-center trial, every surgeon has his own approach. There's also in nerve-sparing radical prostatectomy, you're walking a tightrope between functional preservation and the risk of positive margins. The neurovascular bundles are immediately adjacent to the prostate. You kind of have to shave them off. There's huge nuances in terms of getting into the right plane, different degrees of neurovascular bundle preservation. In general, the wider you go, the lower the chance of a positive margin, and on the other hand, the greater risk of erectile dysfunction as a consequence.
I mean, the best answer I can give as to the relatively high rate of erectile function preservation with surgery, you know, it's all good, is that you know, there's this phenomenon, the Hawthorne effect. Clinical trials influence behavior. My interpretation of the data is that the surgeons knowing that the functional outcome was gonna be scrutinized erred to some degree on the side of neurovascular bundle preservation at the cost of a relatively high rate of positive margins. Now, both of these results are very consistent with many published series. They're not outlier results at all. You've got pretty good erectile function preservation. You've got a somewhat higher rate of positive margins, but they're both really kind of under the mid part of the bell-shaped curve of outcome. Yeah, I.
You know, that's really the best explanation that I can give. I would also say that the one-year data will be somewhat more definitive in this regard. It's very plausible that certainly I'd expect an improvement in the TULSA-PRO data at a year. That's what we saw in the TACT study, that from six months to a year, there was improvement in erectile function. You may see the same thing with surgery, or you may not. You know, time will tell.
Okay. I wonder if I could ask a follow-up.
Mm-hmm.
I wonder if you could help us avoid some improper comparisons between the TACT trial and the CAPTAIN trial. These are different in structure and probably several other parameters. Could you maybe highlight a few aspects of the TACT trial and the CAPTAIN trial that may not be directly comparable?
Oh, yes. Well, the TACT trial, which had good results, but was very much a learning curve trial. This was early days. The trial was planned probably close to a decade ago. At that time, there was a lot about patient selection and treatment boundaries that we know now and didn't know then. For example, the importance of calcifications greater than 3 mm as an exclusion, if the calcifications are anywhere near the cancers, the limitations in terms of volume. The 80% figure with TACT to me is a lower bound.
I fully expect, partly based on my own clinical experience with TULSA-PRO over the last five years or so, outside of any clinical trial, that the oncologic outcome is gonna be significantly better. Now, that's a prediction, but, you know, we know who the failures were in TACT. Periurethral cancer, because the urethra is cooled. If you have a cancer that is within a couple of mm of the urethra, which can happen, that's a recipe for failure. We, you know, we exclude those patients from TULSA-PRO. They should have something else. There are not a lot of them, but they are overrepresented in the failures. The first thing is patient selection. I predict that we're gonna see better than 80%, probably closer to 90% success rate.
The second relates probably to outcome vis-à-vis functional outcome because, first of all, the AI margin assist has meant more accurate delineation of the prostate margin. Probably more accurate preservation of neurovascular bundle, so kind of the same thing applies. It's a question of kind of a learning curve study versus a study where the practitioners are more experienced and, you know, you would expect to see better results.
Thank you, Dr. Klotz. I actually have a couple of questions, submitted online, by Dr. Rajiv Chopra. I'll read those out loud. Dr. Klotz, as a pioneer of active surveillance, how do you feel TULSA will impact the practice of AS in prostate cancer patients?
Yeah. Active surveillance means basically conservative management with intervention for patients whose risk profile changes over time. We are not talking here. You notice there was no Grade Group 1 cancer in patients in this study for good reason. We did have some in the earlier TACT trial. The reason is because most patients, 90% with Grade Group 1 prostate cancer don't require treatment. No one is proposing that this be a routine treatment for those patients. There are a few who do warrant treatment, and it would be appropriate. Where it's gonna have an impact is because as you follow these patients, somewhere around 20%-30%, depending on the series, are eventually re-categorized as higher risk and have treatment indicated.
In some studies, it's more than 50% that reflects mostly the pre-MRI era. What happens in these patients, they are re-imaged. Their MRI now shows progression of a solitary lesion. In most cases, when you re-biopsy those patients, it's Grade Group 2. In other words, it's not a rapidly lethal cancer. It's just progressed to a cancer that we take more seriously. What do you do with those patients? A treatment like TULSA is perfect for them because, again, you wanna preserve quality of life. In most cases, the disease is not that aggressive. I see TULSA positioned as very much a treatment of choice for patients who have been on surveillance and now are recategorized or reclassified with higher grade cancer and need some treatment. Now, a few of them are gonna have very high grade cancers.
That's roughly 5% or less of a typical active surveillance cohort, and they may be better off having surgery or radiation. Although time will tell. I mean, at the moment, the TULSA Procedure is really geared towards intermediate risk, but there's no reason to think that it also can't be effective for higher risk patients once its efficacy is really confirmed for intermediate risk.
Thank you, Dr. Klotz. The second question is also directed to you from Dr. Chopra. Often in RP patients, strategies are implemented post-recovery to encourage and facilitate erectile function recovery. For example, some patients begin taking Viagra before surgery to help with blood flow and recovery.
Mm-hmm.
In CAPTAIN, are both arms of the trial, TULSA and RP, receiving equivalent interventions to control for these types of interventions?
Yeah. The term we use for this is penile rehabilitation. I will say that the evidence supporting the use of penile rehabilitation in terms of actually improving the long-term outcome is not very good. We don't know if it has any durable impact, but it certainly facilitates earlier recovery of erectile function in the patients who use it. We did not specify in the trial the use or not use of penile rehab. I'm afraid we don't have. My guess is that most patients, whether they have surgery or TULSA, if they are interested in recovery or erectile function, will be at least put on a PDE5 inhibitor like Viagra or Cialis.
We will have that data in terms of concomitant medication, but we don't have it as a kind of formal outcome measure, so I can't answer your question with actual data.
Thank you, Dr. Klotz. Now, our next question comes live from Ben Haynor at Lake Street Capital Markets. Ben, if you would like to come on.
Good day, gentlemen. First off for me, just curious on what typically happens with cancer control outcomes when patients do have positive margins, undergoing radical prostatectomy.
Yeah. It's variable, is the short answer. The rate of what is called biochemical progression, meaning the PSA goes down to zero and then starts to rise over time, usually takes about three years before you see that rise. The time to the rise gives you a clue as to whether it's a local recurrence or a distant disease. Remember, some of these patients may have occult metastasis that's the natural history of which is not gonna be affected very much by treating the local prostate 'cause the horse has fled from the barn. That's another piece of this. Overall, about half. It also depends on how extensive the positive margin is, on the grade of the cancer at the site of the positive margin, whether it's low grade or high grade. There's a lot of variables.
Overall, about half of those patients will eventually have a recurrence. Positive margin also goes along with an increased risk of metastatic disease. It's a risk stratifier for a more aggressive type of cancer. It's not a straightforward thing in terms of its significance. Beyond the positive margins, patients with negative margins have a rate both of local recurrence and metastatic disease. It's lower, but it's not that much lower. By and large, positive margins is significant in terms of an increased risk of recurrence either local or distant, but it's not a black-and-white issue.
Okay. Fair enough. If it winds up with the sort of recurrent outcomes, and you're saying that, or speculating I guess I should say, that you know you could see a 90% success rate with TULSA-PRO in terms of the cancer control. Is it conceivable that you could see superiority even though the trial isn't designed to show it for TULSA-PRO versus the surgery?
Well, I'll put my words carefully. It's certainly conceivable. I think that would be a phenomenal outcome from the perspective of TULSA-PRO. I mean, if you do the math and my estimates are correct, then you're gonna see about a 20 or 25% rate of biochemical recurrence after surgery, which is very typical.
Mm-hmm.
Those patients get radiated, and the majority of those patients who are radiated then have a biochemical response and essentially are cured. Of course, there's long-term effects from the radiation and so on. It's, you know, there's trade-offs. It is certainly plausible to me that the rate of biochemical recurrence, if you're just looking at that endpoint, may be higher with surgery than the rate of positive MRI being positive for recurrence confirmed by positive biopsy with TULSA-PRO. Very much so.
Okay, got it. Regarding everyone's favorite endpoint, what do you expect to see with the penile shortening endpoint?
Yeah. Well, the penis gets shorter after surgery. Many people have observed this. No one is really sure why because you're not kind of retracting the penis into the pelvis when you do this operation. You're bringing the bladder down to the urethra. It's probably a combination of decreased blood flow because the penile volume does reflect the blood flow. You know, increased blood flow, you get an erection. It may also reflect some anatomic features. You are not gonna see that with TULSA-PRO. I would be very surprised. My prediction, that is one of the secondary endpoints, is that you're gonna see more penile shortening after surgery than you do with TULSA-PRO.
Got it. Last, for me, I don't know if this is more for Mathieu or Arun, but how do payers kinda look at incontinence, ED, overall health? You know, presumably this leads patients to kinda have less will to take care of themselves, you know, how much does that kinda get factored into coverage decisions, if at all?
Yeah. It's a whole different ballgame there. I'll hand that over to Mathieu or Arun.
Yeah. Thank you, Dr. Klotz. With respect to insurance companies, you know, they have a process, and typically they look for Level I data for comparison purposes. As long as they can see that this trial meets its endpoint, I think that is how they make their decisions. Based upon these results, I think it's pretty favorable. I think we definitely think that even in the near term, you will begin to see coverage decisions from insurance companies based upon these results, in the later half, certainly by Q4 this year.
Got it. Well, thanks, for taking the questions, gentlemen, and congrats on the outcome here.
Thank you. Dr. Klotz, we're gonna give you another short break here, at least one. So this question's from Mathieu, from Brian Gagnon, an investor. Mathieu, based on what you know now, the oncologic information coming later this year, when do you believe is the earliest that TULSA-PRO may be included in the guidelines?
Yeah. Thanks, Brian. That's a great question. As discussed in the presentation, you know, inclusion in guidelines really is a process, and it doesn't kinda go from not included to included sort of overnight. We did mention that TULSA-PRO is named already in the 2025 version of the NCCN prostate cancer guidelines, which was really interesting because it was the first time that the TULSA-PRO procedure was named by name. It was also the first time that the NCCN prostate cancer treatment guidelines within the ablation world really distinguished between whole gland ablation, which is of course what TULSA-PRO does very, very well, to focal ablation, which is a bit more of a crowded space when you look at new technologies.
I think those, even the 2025 guidelines were a really positive step forward, to sort of establish what the TULSA-PRO procedure is and the fact that it can be applicable to whole gland ablation, which really opens up the market to, you know, patients with bilateral disease, and so on and so forth.
To Arun's point, I mean, professional societies and guidelines really do look for that Level I data to have that conclusive comparative analysis which allows professional societies to make statements like, "We recommend this," or "We recommend that." You know, is the six-month kind of quality of life outcomes gonna be enough to get there? Probably not. We're gonna wait until the end of this year when we have the first set of oncological endpoints, as we had discussed with the positive surgical margins, the TULSA-PRO biopsy data, MRI data, PSA follow-up.
We'll start to put that together, at the end of this year, get that published, and I think that will be the sorta next step forward in order to get those positive recommendations for a subset of patients. Our primary safety outcome which is scheduled for 2028, I think will be really sort of the nail in the coffin, if you will, in terms of demonstrating without a doubt, that TULSA-PRO's non-inferior from an efficacy, oncological efficacy perspective, and really superior from a safety and quality of life perspective. Even the perioperative outcomes like the, you know, no overnight stay in the hospital, I mean, these are important metrics for not only patients but to physicians. They don't have to necessarily, you know, do the rounds the next day, and so forth.
To payers. A night in the hospital is quite expensive. From a hospital efficiency perspective, I think those outcomes will also really make a difference.
Thank you, Mathieu. I don't see any more questions right now, so I think we'll turn it back to Arun for any closing remarks.
Thank you so much, everyone. In summary, better clinical outcomes, flexibility to schedule TULSA-PRO days, faster patient recovery, and we didn't talk about it today, but it's in our corporate presentation, better economics for the hospital. Those are the four primary value proposition of TULSA-PRO. Again, better clinical outcomes, flexibility to treat all day, faster patient recovery, and better economics for hospitals. With that, thank you so much for joining us today. We look forward to briefing you at the Q1 call. Thank you.