Thank you. These are my disclosures. I'm a founder and equity holder of a startup company called Neoc Orthopedics, and the bare scaffold that I'm going to talk about today is only FDA approved for use in the clinical trials that we're going to describe. So when we think about ACL repair, one of the things we think about is reliability. So when we look at percent revision surgery at two years out from an index ACL operation, in adults we can expect a 5% or less chance of needing a second ACL surgery at this time point. In adolescents, it's slightly higher, maybe around 20%. But when we think about repair, results are closer to 15% in the lower demand adult age group and as high as 50% in the teenagers. So it's this lack of reliability that's really brought most of us who do ACL surgery back to really relying on ACL reconstruction as our primary surgery of choice for these patients. Why isn't ACL healing reliable with repair? Well, one of the reasons may be that we tend to fix these inflection when we try to repair them and then the patient goes into extension. The ACL is longer in extension than it is inflection, and so if you don't have a good secure fixation or just the biology is not there, you're going to form a gap between the two torn ends of the ligament. And we know that in the ACL, that gap doesn't fill in with anything. So if you have an MCL tear that you've repaired and a gap forms, that gap fills in with a fibrin platelet clot that can go on to stimulate healing in the gap. In contrary, the ACL doesn't form any of that fibrin platelet clot in the gap due to its position in the synovial fluid of the joint. So for the ACL, if we have a repair that forms a gap, we're stuck. So what happens is eventually our sutures are going to break down and the repair will fail. So we thought, can we make ACL healing more reliable? Can we fill the gap in with something that will make it so there's not a gap in the ACL and allow the ACL to heal? So we worked for a while developing the appropriate scaffold to put in that gap. And if we want to encourage healing in the gap, this requires testing specifically for this function. So this is an FDA requirement. So in order to be in compliance with the FDA, you have to do certain things for this function. So this is requirements like you have to show that your scaffold is conducive to ACL cell migration. You cannot use a barrier tissue for this function. You need to show it has an optimized resorption profile in vivo. So you want your scaffold to resorb at a rate that's balanced by new tissue formation. Not too fast, not too slow. And you want to minimize the immunogenic reaction. So you don't want to see any adverse reaction in the ligament and you don't want to see any synovitis. You also want to end up with good strength of your healed ligament. So this requires careful tailoring both of the components of the scaffold and your manufacturing process to achieve these goals. So we went through and did that and developed our scaffold and tested it in a large animal model. And what we found was that the ligament histology of the ACL is restored after treatment with this scaffold enhanced repair. We also found that a scaffold enhanced repair led to strength that was better than suture repair alone and equal to that of an ACL graft in these animal models. We also found that treatment with the bridge enhanced ACL repair preserved the cartilage surfaces in these large animal models. So at a year, if you take an animal's knee and you cut the ACL and you let it walk around, this is what its medial femoral condyle looks like at the year time point. If we do an ACL reconstruction in that same model, again, we see this breakdown of the cartilaginous surfaces, particularly in the medial compartment. Very similar pattern to what we see in our patients with ACL injuries. If we did a bridge enhanced ACL repair, though, we did not see the cartilage breakdown. So this type of data, we were able to submit to the FDA and get approval to do the BARE-1 study. The surgeon on this trial was Dr. Lyle Michele. He did this as I was in conflict, as I mentioned before. We ran this as a cohort study. So 10 patients had the bridge enhanced ACL repair and 10 patients had a hamstring graft for an ACL reconstruction. The inclusion criteria were patients had to have a complete mid-substance ACL tear, ages were 18 to 35 years of age, they had to be no more than 30 days from injury to surgery in the BARE group, and all meniscal injuries were included except for bucket handle tears of the medial meniscus. The results of this study showed there was no revision ACL surgery required for patients in either group at two years. There was no evidence of infection or rejection in either group. There was a 20% risk of additional surgery in both groups. One patient in each group required a partial medial meniscectomy. One patient in the BARE group required removal of the tibial button, and one patient in the ACL reconstruction group had an arthroscopic procedure to treat arthrofibrosis. As far as patient reported outcomes, we evaluated the IKD subjective score. Age match norms for this score are 88 points. The ACL reconstruction group in this study came in at 85, and the BARE patients came in at 92. We evaluated the AP laxity of the knee using KT1000 testing. Uninjured knees typically are less than one millimeter difference between the two sides for patients. Other trials for ACL reconstruction have reported this to range from one to three millimeters, this side to side difference. In this trial, the ACL reconstruction patients had a 3.3 millimeter side to side difference. The BARE patients came in at 1.9 millimeters. We also evaluated strength of these patients, particularly hamstring strength. Our ACL group was found to have a deficit persistent out to two years. Bridge enhanced ACL repair patients did not show this deficit. The ACE BARE was found to be similar in size to the native ACL as well. So we know that the intact ACL is about 50 square millimeters in cross-sectional area. The ACL reconstruction graphs were 50% larger still at two years, whereas the BARE ACLs were similar in size to the native ACL. In terms of orientation, the uninjured knees in this cohort had an average orientation sagittal angle of 49 degrees. Reconstructions were 56. BARE subjects came in at 50, very similar to what was seen in the intact ACL. So in summary, our results showed that we had no infections, rejection, or failure. No gap formation was seen in these subjects treated with the scaffold enhanced repair. The two-year results showed our BARE subjects had good patient reported outcomes, good knee stability, better hamstring strength, and restored ACL anatomy. Our conclusions are this was a small first in human study. We saw no adverse reactions to the BARE scaffold, and so we believe this method is deserving of further study. We have three additional studies going on now, the BARE 2 trial, BARE 3 trial, and MOON BARE trial, and we hope to be able to report on those to you in the future. Thank you for your attention.

scaffold

ACL repair surgery

ligament gap

healing promotion

scaffold-enhanced repair