Maurice Sarano, Valthera - Innovation for Valve Regurgitation | LSI Europe '24

Maurice Sarano 00:02
Thank you. It's my pleasure to present on behalf of Valthera our value proposition, which is a transcatheter tricuspid valve replacement. Brief introduction, the tricuspid valve is on the right side of the heart, and when there is moderate or severe tricuspid regurgitation, there are devastating consequences with renal, heart, and liver failure leading to reduced quality of life and high mortality. You see, this is one of the survival curves, and around three years, there is 50% mortality occurring in these patients. So the medical treatment is very limited. It is transiently effective; surgery has a 10% operative mortality with a high recurrence rate after valve repair. So that in clinical practice, 95% of the patients who have moderate or severe TR are never operated on, never treated surgically, and there is a big unmet need for treatment. The unmet need for treatment that I present here is based on the publication related to the work that we have done on tricuspid regurgitation, showing that there are approximately 200,000 new cases per year in the US, and probably around 300,000 new cases in the EU, so a very large mass of patients that are never treated. And anyway you turn, the percentage of patients who will be treated, the market size will be more than 1 billion in the US and in Europe, taking into account the cost of goods made, it is between $100,000 to $1,000,000. It is a highly interesting field to do now.

What is the panorama of treatment for tricuspid regurgitation? On the right, you see the cable treatment, and the cable treatment on the left, you mean it's heterotopic valve replacement, and it's palliative. We're not interested in that. We don't believe in that. At the bottom, you have the various repairs, and these repairs are difficult because they need not just an intervention of high quality, but an imager of high quality. Not many centers can do them. And when you do it and you think you have had success, two-thirds of the patients have residual tricuspid regurgitation, moderate or severe. So it is too ineffective to really treat the number of patients. So the preference now is at the top. It is orthotopic valve replacement, inside the valve itself to have a valve replacement. The only one that is currently approved is the Evoke of Edwards, and when you look at their site, it looks like it's snug and nice. Now the reality is a little different because the anatomy is very large of the defect, and you need to insert a very large prosthesis. Because of that, the introductory system is very rigid. You have heart perforation during the positioning. You have trauma to the heart, to the septum, and these people have AV block, or they have right ventricular dysfunction.

So the reality is this: it's a very large device, traumatizing the septum, traumatizing the RV free wall, so you have AV block in 30% of people who do not start with a pacemaker, right ventricular dysfunction, canting if you don't put the device right with the grippers at the same place, and a very large device, so that you will have slow flow and thrombosis formation in the prosthesis. So we clearly need something, and all the other devices existing have the same umbrella-like design that leads to the same type of problem because of the size of the device. Our device here to guide you on the left side, the heart is seen from the left-sided cavity. On the right side, the right-sided cavity, our prosthesis is in the center, and when we zoom in on it, we see the prosthesis that has considerable advantages, unique characteristics, proprietary anchoring, slim conical prosthetic shape, and supra-annular design that doesn't press on the annulus. Because of that, you have a steerable valve without the possibility of canting. Native leaflets are covering the frame and allowing the absence of periprosthetic regurgitation. There is no impingement on the septum or the right ventricular free wall, and the flow is smoothly accelerating through the prosthesis, preventing clot formation in the prosthesis.

With this advantage, here is our animation. We come from the superior vena cava, but we can come from the inferior vena cava. The first sheath is placed, the second sheath enters the right ventricle. We place one and then two, and then three anchors into the thick interventricular septum, and the tethers that are left in place guide the valve into position; we then lock it in place. When it works, it works immediately, opening and closing with the function of the right heart. When you see from above, the shape and the supra-annular position explain why we have no trauma to the septum, no trauma to the RV free wall, and we have a unique design that will allow the patients to recover their cardiac function. Here is the prosthesis constructed from porcine tissue, with fabric around for the skirt, and it has major advantages compared to all the techniques we can discuss later. But major advantages here are the reanimated heart experiment that we did, where you see the valve deployed and the leaflets functioning in position. To the right is an echocardiogram. So for those who are not cardiologists, I'm going to explain that you see the prosthesis as that cone that you see on the right side, and you see that the supra-annular position is reached by the prosthesis exactly as we planned to do it. The blue flow shows that the flow is accelerating, washing the leaflet, but doesn't go too high. There is no obstruction. So we achieve what we want, and around you see the muscle that is contracting. It's the right ventricle contracting and having no interference with the rhythm, and excellent ventricular contraction preserved because there is no impingement.

So a real unique one, our intellectual property. We have a patent in the US. We are in the office section in the European patent, and we have a Japanese patent in rebuttal stage. So we're very well placed. The path for regulatory approval is very well defined. Because Evoke was approved on a single-arm trial, we will not need to have a 400-600 randomized trial. A single-arm trial will simplify the approval, and there is already a DRG and CPT code existing. So the path to commercialization is very well defined. This is our timeline. We are doing what you see at the top left: the bench testing to verify that nothing breaks, and we'll have those results very soon. In 2025, we will finish the application for the FDA, and we'll be in a position to start our first in human trial, and then start the following year, the pilot clinical trial with 20 to 40 patients. Just as a reminder, the InnoValve that was sold to Edwards this year, very recently, was sold after a 20-patient series done at the Mayo Clinic. So we think we can do better. We can do better than that and have a valuation inflection very soon.

So this is the comparison with the recently completed acquisition. You see that the valuations that were reached for mitral and tricuspid replacement devices have been quite rich, and we believe that we can attain or overcome this kind of valuation with our device that will be the best tolerated in the market by the patients. The team: we are lucky to have the best experts in the world in our team, and to have contractors that have done an outstanding job of producing the devices. In summary, the problem is TR. It is currently almost never treated. The solution is tricuspid valve replacement, transcatheter, and we believe that we have the best transcatheter replacement that can be done, and we seek funding to conduct the preclinical testing so that we can go to our first in human. Thank you so much for your attention.