Video Transcription
Boris Keweloh 00:02
Bacterial hypertension is the world's most common disease. It's every fourth person suffering from it, and despite modern medical thermal therapy, many patients, like 1/3 of the patients, still remain with high blood pressure. So the second option to treat arterial hypertension is renal denervation. But current renal denervation devices have kind of failed, or they are insufficiently treating the disease. And this is why we started this technology I'm going to talk about now, CryoVasc. Our mission is to bring a much more potent renal denervation device to the market using icing. So what's renal denervation? Renal denervation is the idea to cut through the autonomic nerves, which sit on the arteries going from the aorta to the kidney, and which regulate hypertension. This idea is like 15 years old, and a decade ago, there was a real gold rush in the industry with that technique. It was like 15 companies building devices, and all that was because of two very good trials, Simplicity Hypertension 1 and 2, which showed decreases in blood pressure of up to 32 millimeters of mercury, and which were well conducted and tested renal denervation trials. A third multi-center sham-controlled trial done by Medtronic, which acquired one of the startups, Arden, totally failed, and the trial crashed the whole field. And when I was seeing that as a physician a decade ago, I couldn't believe I witnessed such a thing that the technology which works, which is already proven in animals and patients, then by a single sham-controlled trial, totally fails and everybody drops it. I couldn't believe that was happening, so I started to go deeper into that. What's wrong here? The trial was badly conducted. It was just two to four patients per center. The investigators were not experienced enough. They had done that two or three times too late. They were no EP guys. They didn't know what to do, and denervation was not tested. So now, for a decade, the industry has really tried to re-establish the field. And the two remaining devices, which are still on the market, mainly, and which are FDA approved, are Medtronic's Spiral and Recor Medical's Paradise device. And the results of these devices are poor. This is from the current publications and guidelines. On the left two bars is the Spiral. The right two is the Paradise catheter, and what you see is only a reduction of blood pressure from five to 10 millimeters of mercury. So which patient in the world suffering from arterial hypertension will have a one-hour procedure with stitches in his groin arteries for a reduction of 10 millimeters of mercury pressure? None. So the field failed. So what's the problem with these devices? They are not strong enough, in our opinion. They don't test denervation, and in the case of the Spiral, they only give like five radio frequency spots around the artery. The idea is that the longitudinal nerve fibers on the artery, that every nerve fiber will be cut at once. But it doesn't work because it's not longitudinal fibers. The fibers are a network. They cross, so it can't work. As an EP guy, I know this difference very well because I'm treating every week patients with icing, that's a cryo scar on the right side, and with radio frequency. That's the scar on the left side. So if you use radio frequency, that's like trying to burn one room of a house, right? Having a fire. You see a thrombus on top of that scar. There is bleeding in the scar, and the scar is not well demarcated. In contrast to that, the cryo scar, the endocardium is intact, well demarcated, no bleeding, no disruption. So a cryo scar can be much better controlled. And this is where the whole idea started. If you use cryo technology, you can make much bigger scars in the renal arteries without the four problems of disruption of the arteries, stenosis, thrombosis, and kidney infarction. So I looked into the literature. Had somebody done that? And yes, so there are 11 patients published already a decade ago. Everybody forgot that, but it's done. It's a group from Jena in Germany, and they used Medtronic's Freezor Xtra in an off-label use. It's not a balloon, but it also gives us a nice ball to ablate. Patients who before had a failed radio frequency ablation, and it's very impressive, their results: ambulatory blood pressure reduced from 183 to 130, that's the 11 patients. And that's my most beloved single case study, which I found when I was looking into that. Now, eight years ago, I talked to the physician who did those two procedures, and that guy is still alive, it's an old man. He suffered from arterial hypertension, and he had 190/220. They would do a radio frequency ablation. First pressures would drop. Then something happened, which we don't know, the nerves regrow. So pressure went up again. And then after a year, they would dare to do a cryo procedure with Freezor Xtra, pressure would go down. And after three years, there's even a late effect. Impressive and even more impressive, this is his drugs: seven, six drugs in the beginning, down to five, up to three, and after three years, he's at zero. So what has happened here? Cryo has some kind of late effect, and a physician whom I know, a neurosurgeon, can tell the same story if they ablate nerves with cryo; there is a longer lasting effect than with radio frequency. Yeah. So this is a picture of the balloon reconstructed. It's simple. It's a big cryo balloon. It's three centimeters long, so it'll fit into the main stem of the renal artery. We don't want to go into the small branches because we want to keep the procedure simple. And it carries electrodes. Why that? This is to have a non-point. What we do is we do a high-frequency stimulation before at the beginning of the procedure, which makes blood pressure rise 15 millimeters of mercury, about then we do the ablation. Blood pressure drops a little, and then we stimulate again. And if there is no more rise, the nerve is disrupted, right? If there is still a rise, still a rise in blood pressure, we would ablate a second time. So even an inexperienced investigator will have an endpoint. And this is what we do in EP; we don't just ablate somewhere. We ablate up to a certain endpoint. And yeah, so I
Boris Keweloh 07:44
we did an animal trial, we could see in histologic preparations that we do disrupt the nerves at the different layers of the arterial wall and also deep inside the wall. One thing, and the second thing in the animal trial, we analyzed kidney concentrations of norepinephrine. This is like the end of the nerve as a neurotransmitter, and it's well established that the decrease of norepinephrine in the kidney is clearly correlated to whether the nerves are cut through or not, and we found up to 80% decrease of these values, which is in the absolute upper range of all published data of the competitors. Yeah, so some business figures: the device is going to cost something. Half of it is costs. No problem to make money with that. That's almost a no-brainer. The market is as big as possible; even with very conservative assumptions, we end up at a very high number of patients, and we have been financed by the German state with a convertible loan of 2 million euros, and are now doing a Series A round to raise 7 to 8 million euros. We have already raised three and a half and need another four to five, and we want to come to a real hard endpoint, which is not some technical things, but which is to clearly show a bigger, a much bigger decrease in hypertension in patients. So we'll do a first-in-man study with 40 patients, and even compare that to the competitors. Our team consists of two physicians, one technical, one science guy, one finance guy, all very experienced, and I'm very happy to have Felix in our advisory board, who is the guy in the world who has published by far the most of the renal denervation literature and work. Thank you very much. Thank you.
