Paul Molloy, Applaud Medical - Low-Power Ultrasound Lithotripsy System | LSI USA '24

Paul Molloy  0:03  
I'm going to talk to you about the world's first office based kidney stone treatment. It's not laser, it's not Shockwave. It is founded on a new mechanism of action we call acoustic cavitation. And the enabling molecule is licensed out of Caltech. You'll see the founders are from Stanford and UCSF, the microbubble allows us to use very low sources of energy. And that eliminates the need for anesthesia. Our catheter system, which delivers the micro bubbles, is very elegant, it's smart, and it's sensing and allows us to eliminate fluoroscopy. You take those two things together. That's what gets us into the office. This is the molecule. For those of you who are chemists, and I'm not we do have PhD chemists on board. This is an mRNA vaccine delivery vehicle. It's a drug delivery vehicle if you like as well, we have an inert gas inside it. On the outside is a ligand with a bisphosphonate tag that's negatively charged, it has an affinity for calcium, or magnesium, anything positively charged and tracked as lots of calcium in kidney stones, probably 90% of kidney stones have calcium in them. Therefore, when we put micro bubbles in the ureter, they want to be near the kidney stone. And the external source of energy can cause those micro bubbles to do the work for us comes as a dry powder. its shelf life to five years at controlled temperature two years at room temperature. And it's just reconstituted with regular water or saline for injection, we deliver half milliliters in several doses over the course of 30 minutes. But that expansion and contraction releases micro jets of energy on the stone, which I'll show you. And it's a device because that mechanism of action is entirely mechanical. There's no chemical activity going on here. There's no bio excretion or absorption going on. There's no physiology whatsoever. So it's purely mechanical energy. Think about it as tiny depths charges on the stone. And that mechanism of action is quite revolutionary. This is what it looks like if you can click play for me it was that happened here. There's the catheter on the top squirting the micro bubbles in looks like cigarette smoke. The ultrasound is invisible coming from the side was tiny for 10 nanometer bubbles are in all the cracks and crevices. And they're expanding and catastrophically collapsing and releasing energy and degrading the stone into fragments which are naturally excreted. So there's no confirmation required. We in our studies have shown that we get the stone particles down to naturally executable sizes with a 30 minute office based procedure. Obviously patented not just the microbubbles and the molecules that we tacked to it but also the manufacturing process and the cost of goods. The smart catheter that we use to deliver the microbe was also patented along with the other hardware. I won't get into too much detail here. But it's issued not just in the United States but in Europe and China and other countries. This is how it looks in the office. The patient, procedurally sedated conscious sedation you might call it that means could be nitrous oxide, like your left it could be midazolam, but no general anesthesia, no anesthesia team, the doctor standing at the bedside and the console on a cart, the ultrasound probe locked in place with an arm with a single universal ball joint lock. The catheter and the head talk to each other. So once we get pairing in an acoustic window, foot pedal actuation very straightforward to use. And train takes a couple of hours to train a doctor to do this. And there's a single use tray that goes with it per procedure. So the tray consists of a catheter and the microbubbles, the fluidics and some accessories, that's going to be highly priced. It costs about $200 to make in the United States at this time, the way our reimbursement and coding is set up we think we can sell it for about $2,500 per procedure. And because we're eliminating all these costs the anesthesia team fluoroscopy the in hospital procedure time, it's still a win win for payers, both Medicare and private payers, and it pays the physician more than they're paid presently for laser or ultrasound procedures like Shockwave. This is the catheter This is our own design and pattern doesn't exist anywhere else it goes into your order. So same size as a regular Bumblebee urologists have really no difficulty placing this. There's no ureteroscopy if you can visualize the urinal orifices just a guide wire, the catheter goes over the wire. So anybody who can do Cystoscopy can do this procedure. And then the catheter talks to the ultrasound probe and tells the user that it's okay to fire. And it's really that simple. This is a raster scan of the transducer head in action. This is a very, very unique beam shape. It's not high foo. And that's very important because we don't have to get a laser pointer on the stone to destroy it. We're not trying to destroy the stone we're trying to actually bubbles and it's been because it knows the stone to distance we have time of flight and we have those sensors on the catheter. We only have to get the stone in the box. It's a six and a half by three centimeter box it eliminates the need for perfect accuracy with catheter placement. We just have to be roughly in the vicinity of the stone In order to get the stone in this been here and then our 12 transducers on that phased array transducer head, bathe the micro bubbles in energy, they cavitate and they destroy the stone. It's very elegant. It's very powerful. And it's very easy to use. Market obviously, if you know kidney stone disease is gigantic, many, many sources of data here, this is World Health Organization, but 10 to 13% of the population of the earth have a lifetime incidence of 10 to 13% Stone belt. In countries like India, it could be as high as 15%. That's very much water and lifestyle related. If you take that into numbers divided by 75 years, 11 to 14 million patients per year eligible for treatment. Now they're clearly underserved is about 2 million ER visits in the US every year, only about a million of those goes to treatment, typically PCNL, laser or Shockwave. The other half are watchful waiting patients, they just don't get anything. They're told to pass this stone, they get opiates while they're waiting. So a huge underserved market 50% underserved in the US maybe 80, or 90%, underserved in many, many other countries. And we solve for that problem. This is not getting better, it's getting worse as our population ages as Climate and Water problems materialize. disease incidence is going up, it's already skyrocket in the United States and other countries are much worse. This is a time and motion study from SUNY just for California, we looked at how long it takes to get treatment, we looked at how far patients have to travel. And we looked at outcomes, terrible standard of care between, say rural farmworkers in California and urban elites average of 100 miles to get treatment. And then after several weeks, still more than half the patients not treated. So of course, I can get treated at UCSF with Dr. Stoller within a few days. But if you live in Fresno and you are a farmer, it might be four weeks during which time you may lose your job, suffer financial toxicity and so on. So the health equity health economics healthy quality issues are very, very fundamental to the value proposition here. We've treated 174 patients so far, both randomized and single arm studies can't really show you a lot of the data because it's embargoed. It's been presented for poster at AOA, there'll be a podium presentation, I can tell you that it's good. It's far superior to existing Shockwave. And it's certainly non inferior to laser in terms of outcomes. It also has a much lower adverse event profile, which you would expect because the ultrasound energy level that we're using is low pressure, it's one to four mega Pascal's at best compared to say 50 Mega Pascal's for Donia system 30 to 50 watts for lasers, there's no thermal damage, there's no acoustic shock damage, there's no hematuria, there's no bread and no bruising and there's no pain. It's a gentle system. And the clinical outcomes are already on par with what's available, except we make this available in the office not in the hospital setting. On the left bar is our genuine system from that first in human study in Australia, you can see that the mass loss is already quite material, the brios system here over on the right is superior to that it's actually six and a half times more powerful than our first inhuman system that I just showed you the data from the y axis here is mass loss in grams. So we literally degrade the stone, measure how much the stone mass is degraded over time. And on the x axis on the bottom, you can see that mega Pascal cells. So the Australia data was done with diagnostic ultrasound, we know that that doesn't do anything. And therefore it's only explainable by acoustic cavitation, which is what causes the fact we're going up a little bit because we do get optimal acoustic cavitation in this four to five range. Above that you start getting spontaneous cavitation and shielding, it doesn't really make sense to go higher, you actually get diminishing returns with higher pressures and the patient starts to feel it. So this is the the ideal range. And there's a lot of science in the science team here to validate that large market hasn't really moved a lot in the last 25 to 30 years. Obviously there's franchises in Shockwave, a lot of capital equipment out there. There's franchises with laser fibers and ureter scopes. But the last 30 years, you have to go to a hospital see a specialist wait four to six weeks, we're about to disrupt that. We've talked to FDA and CMS both about the regulatory pathway and reimbursement. This is de novo device pathway. We're about to submit our IDE for the pivotal study. It's a simple single arm study the reimbursement pathway in the ASC HPD setting cat three code moving to cat one over time, but more importantly in the office setting, very likely an APC level 540 $900 payment $800 for the physician $2,500 For a single use kit, and everybody wins it's still more payment for the physician then in the hospital. It's still lower price for the payers than in the hospital. And the patient gets access Monday instead of four weeks from now anywhere with his urologist or hospital to treat them. So we have access to all the major markets. We have strategic partners lined up for China, India, United States. We will analyze the sales model once we get our approval which should be this time next year and the series ALMS gets us to that. To that border we have a device ready for clinicals. The commercial device will be part of the uses of cash for this round here. This is the team. I was long I met Hopcroft, chemistry and systems engineer Rojgar Altra. from Stanford two exits behind him recently with Johnson & Johnson and declarent This is my fifth startup. I've sold three of the last four companies. I've been involved with public company settings as well. So it's a very experienced team didn't mention our professors from from UCSF and Stanford on our board or the physicians advisory board very prestigious. It's, it's ready to go and it's coming to the cruise ship and mash 10 or small hospital near you this time next year. Thanks very much.