Daniel Levangie, CereVasc - Endovascularly Implantable CSF Shunt | LSI Europe '22

Transcription

Daniel Levangie  0:00  

I'm delighted to be here to tell you about our company CereVasc. CereVasc is a clinical stage medical device company focused on neurosurgery space. Our first target is the treatment of patients with hydrocephalus. It's a very large opportunity estimate. So are the prevalence of hydrocephalus in the United States is about a million patients. The current standard of care is a 60 year old standard, which requires open surgery and has an extremely high rate of failure. We have a very different approach in that we've developed a novel endovascular approach to the treatment of these patients. We have clinical data that looks really strong, very good safety and early efficacy data. There are multiple inflection points over the next 12 months, including an IDE for a pivotal trial in the United States. The management team is a team that's been together for more than 20 years, in some very successful companies that you may have heard of sector cooperation, exact sciences insulet Corporation. And finally, we've got we've spent a lot of time and effort in building the IP portfolio around what we do. Hydrocephalus is again affects an estimated 1 million patients in the United States there are two general forms. Obstructive and communicating communicating Hydrocephalus is the predominant variety, representing roughly 80% of the cases. The etiology is can be congenital, can be acquired as a result of head trauma, subarachnoid hemorrhage, and then a very large population of the elderly are affected with a disorder characterized by ventricular enlargement and a triad of symptoms. That's very distinctive. And because of the standard of care, excuse me and the rate of failure. Many of these patients go untreated, the symptoms of hydrocephalus begin with headache, and then become be escalated to eventually death if it goes untreated. And communicating Hydrocephalus is a disorder of absorption. Each of us produces roughly 450 milliliters of cerebrospinal fluid per day, that's produced by tissue that line the lateral ventricles of the brain. We can only accommodate about half of that. So there's an absorption that takes place of this excess cerebrospinal fluid that occurs through structures called arachnoid granulations. And these are outcroppings of the arachnoid layer of the brain that allow cerebrospinal fluid under pressure to pass from the subarachnoid space back into the venous system. So it's a pressure driven one way valve called the arachnoid granulation that allows for you and I to maintain normal intracranial pressure. Again, the the prevalence is estimated to be about a million patients in the United States, more than 80% are in the category of communicating hydrocephalus. And the largest segment again is this elderly population that has been tricolor in large men and have a very distinctive triad of symptoms. Excuse me, that is recognized generally by the by the general practitioner, the neurologist and the neurosurgeon. The current treatment for Hydrocephalus is 60 years old, involves shaving of the head incision in the scalp burrow hole in the skull, a catheter passed down through the white matter of the brain into the lateral ventricle. That catheter is then attached to another catheter segment attached to a valve that's placed under the skin typically behind the ear. And then a long tunneling procedure takes place across the chest and abdomen, where the distal end of the catheter is left. Excuse me in an incision in the peritoneum. So cerebrospinal fluid produced in the ventricle passes under pressure through this long catheter system and is reabsorbed into the peritoneal cavity. The failure rates that you'll see in the literature are anywhere from 40 to 50%. Within the first couple of years, patients require either an entire replacement or revision of components of the system. And the complication types are listed here, obstruction of the catheters that takes place, ventricular catheter misplacement at the time of the initial surgery, over drainage, which is a particular problem in the elderly, that when the patient changes position from lying to standing, there's a negative hydrostatic pressure that occurs within the long catheter that drains too much cerebrospinal fluid. Infection is a really difficult problem for these patients in that they have meningitis. They they're admitted to the ICU, they have the system disconnected they drain CSF to the bedside through that ventricular catheter. and they're on antibiotics for several weeks. So it's a very a particularly difficult complication. And finally, there are mechanical failures that occur simply as a result of patient movement and growth. Again, the literature is is, is very complete in terms of tracking the performance of the ventriculoperitoneal shunt that I described. Again, it's a 60 year old procedure. So there's a lot of data out there about the rate of failure. But most neurosurgeons will agree that the failures are anywhere from 40 to 50%, within the first couple of years, so our approach is to convert this open surgical procedure to a minimally invasive endovascular approach. And this is our device. On the right hand side is the device it's three centimeters in length. It's designed to mimic the function of the arachnoid granulation. We place this in a dural venous sinus at the base of the brain with the the anchor portion in the subarachnoid space, and the catheter that allows the drainage of cerebrospinal fluid that that resides in a venous outflow at the base of the brain. So again, it's its overall design is to mimic the natural function of the arachnoid granulation. We place this in a dural venous sinus at the base of the brain that's well known to interventional neurosurgeons and interventional practitioners. It's called the inferior petrosal sinus, we have one on either side, you can see the device depicted in the center of this slide as it's placed at the junction of the jugular vein and the IPs. And on the on the left hand side of the slide is a cross section of the inferior petrosal sinus, again encased in blunt bone with a taut Dural, a layer of dura at one aspect, which is opposite a large system of cerebrospinal fluid. So we navigate to that location, we deploy our device across the dura, and we allowed cerebrospinal fluid to pass under pressure from the subarachnoid space into the venous compartment. We believe that we can address many of the failure modes of the VP shunt by reducing the incidence of infection obstruction over and under drainage and mechanical failures. And as a result, do what what has been done in many other fields in converting open surgical procedures to minimally invasive procedures, like the one that we're about to introduce, excuse me. From a clinical standpoint, we've conducted a first in human study, we've got great, very powerful and compelling safety and efficacy data from that study. We use that to support an IDE for pilot study in the United States, we actually have three protocols open currently enrolling patients, and our expectation is to file an IDE with the FDA in the first half of next year for a pivotal trial. In the United States, we expect that that will be a single arm study. compared to historical control. As I said, the VP shot the standard of care is 60 years old. There's a lot of data supporting the performance of that technology. So we believe FDA will be open to a single arm study. In terms of our first in human study, we had to demonstrate that our device did what we said it would do and that is lower, elevated intracranial pressure. So we selected patients with acquired communicating hydrocephalus. So starting on the left, these are patients who have a ruptured cerebral aneurysm. That aneurysm is treated typically by an endovascular practitioner by with coiling. That patient then has a drain in place in their ventricle that drains blood and cerebrospinal fluid for a period of time within that drain is an intracranial pressure monitor. And after about a week, the doctor clamps that drain if the pressure remains normal, the drain is pulled if the pressure remains elevated, they'll unclamped the drain try again in a couple of days. So in these patients that have developed communicating hydrocephalus as a result of the aneurysm, we were able to monitor ICP intracranial pressure following the placement of our device. And this is our first patient treated this is this is really kind of a historical patient in that no patient has ever been treated before without open surgery for hydrocephalus. So this is an 84 year old woman. She had a ruptured MCA treated with coiling. She, she developed communicating hydrocephalus. And as you can see on the chart on the left hand side at the time that her ventricular drain was clamped, her intracranial pressure was nearly twice what's assumed to be the normal level which is 20 centimeters of water. And at the time that our devices placed you can see a rapid decline and ICP and then a maintenance of that, that normal intracranial pressure Over the next 36 hours, which was the primary endpoint for this study, we have five additional patients in that first in human study that have the same pattern. We also have a pilot study in Argentina, in patients with normal pressure hydrocephalus. And we have really very strong clinical results that show improvement in the three the triad of symptoms that I mentioned, impaired gait, impaired cognitive function, and urinary incontinence. I'm a little bit over time here. Let me just go to the clinical strategy that we have, again, is to complete these pilot studies file an IDE with the FDA in the first half of 2023, conduct our pivotal trial and gain FDA approval in 2024. And we're now in the process of a series B financing with a goal of raising $50 million. This is the use of proceeds we have a lead term sheet that we're negotiating. And so I think we're well on our way to actually raising this, this round and funding the further clinical development of our of our technology. Thanks very much.