John von Benecke, Locate Bio - Orthobiologics for Orthopedic Surgery | LSI Europe '22

Transcription

John von Benecke  0:07  

So hi, my name's John, I'm Chief Executive Locate Bio. There are two things I think locate do better than anybody else in our industry. One is programmed drug release, and the other is building instructive tissue scaffolds. And we bring those two different capabilities together to create really exciting combination products. And in this short presentation, I'd like to introduce two of those pipeline products that I think really exemplify our capabilities in the space. As a company, we are proud to be developing products that can relieve suffering, and improve the quality of life for the 1.7 billion people around the globe who suffer from musculoskeletal conditions. It's the third largest area of expenditure in the US healthcare system. And low back pain is the number one leading cause of disability in 160 countries around the world. Now, pretty much everyone here today will have suffered from some degree of low back pain at some point in their life. But for most of us it would have been transient right really saw but didn't last very long. For other patients, that pain never goes away and gets progressively worse as they age. And that's because they could be suffering from conditions like degenerative disc disease. Now the discs the shock absorbers your spine, they start to dehydrate as you get older, that loses disc height and can put pressure on the facet joints, the back of the spine of the nerves coming out of the pain, spine causing incredible pain, they'll start your unconservative. Lifestyle changes then move you to very powerful, highly addictive painkillers. But ultimately a surgical intervention is going to be required to restore the disc height and stabilize that spinal joint. In most advanced healthcare systems, you'll likely receive one of two product types During that surgery to create bone to restore that joint. So it can be a growth factor. That segment is dominated by infuse it was an incredible product launched 20 years ago, it still dominates the entire bone graft landscape. Tremendous amount of bone has grown with that molecules BMP two very powerful therapeutic protein. But it comes with side effects, difficult for the surgeon to handle and a very, very high price point. And the surgeons don't like those negatives, they're likely to result to demineralized. bone matrix products which come from cadavers also have their issues, but really easy to use and much more affordable for our healthcare system. Together, those two products account for a market segment of about $1.6 billion. And we're developing LD graph to take equal share from both of those segments simultaneously. We're doing that by reusing the same molecule as infused that BMP to therapeutic protein but addressing where we think they made some mistakes, and benchmarking ourselves against the good handling and acceptable price of the DBM segment. So to understand how we're doing that, you need to understand where we think infuse got it slightly wrong. So in their ideal conditions, and this is Medtronic spoon data and the ideal conditions at a low pH and a 15 minute soak time, they can get around half of that protein tightly bound onto the surface of a collagen sponge. Using heparin binding domain, the others is much more loosely bound using a surface charge that we know that BMP behaves differently at physiological pH than it does in their ideal 4.5 ph. BMP two says aggregate it loses negative surface charge and it crashes out of solution at physiological pH. And as a consequence of that we're tronics own data suggests that there invivo half life is only around two days, think about how long it takes to grow, but a bone and you can see there's a clear mismatch between the biological need and the bioavailability bioavailability of the molecule. We overcome that because we don't deal with surface attachment, we encode the polymer that the protein within a polymer, so it's buried in there and the body can't get at it until we start to degrade the polymer, which we do over a number of weeks. BMP is then released into the micro environment where it can do exactly what it is supposed to do. This is a cell based assay. So you see cells responding to fresh release BMP over time, the shows out that the release goes well beyond four weeks. And as a consequence of us holding the dose in the therapeutic window for much longer. We're confident that we can down dose This is an industry expected accepted spinal fusion model you see infused in the middle there grows a lot of bone relative to the negative control, but you see us matching their bone growth or just 1/10 of the dose. This is just breaking data. Our data is emerging this month or next month from our large animal studies. This is the final preclinical step before moving into human clinical studies next year. It's it's an amazing image. This is a sheep spine just to orientate you the two big bits of bone that you see there are the vertebral bodies, the disease, this could have been in between them that's been removed and a bridge has been created using our product. So in just three months, it's going from being a product to mature fully integrated bone. You see none of the side effects that you often see with BMP products, no osteo lysis no bone cysts, no ectopic bone growth that's programmed drugless for us. So really excited moving forward. The other product I'd like to quickly talk about in the next couple of minutes is earliest stage for us, but I think has the potential to revolutionize the way hundreds of 1000s of patients are treated. So The product we're developing specifically for orthopedic biofilm infections, it's one of the most challenging areas of medicine for orthopedic surgeons to overcome can happen anytime that you have non viable tissue or an orthopedic implant placed, then there's a race for the surface between bacteria on one hand, which if they can establish a colony and create a biofilm, that means the systemic antibiotics, which is the mainstay of so much of our medicine are no longer effective. And we have to roll back to a much earlier time of very, very aggressive surgical treatment. This is already a very big problem. It's a big problem in trauma with bone breaks through the skin and collapse bacteria. It's a big problem in diabetic foot infections, which then spread up to the bone. And that's certainly a growing area. It's also a problem for blood borne infections, common among IV drug users and a very, very big problem for prosthetic joints. So artificial hips and knees. The chart on the right is the forecast number of hips and knee, artificial hips needs to be implanted in the USA over time. And that's just the USA and every single one of those implants carries between one and 2% infection risk. The consequence of the patient of guessing an infection there is devastating, they're now looking at multiple surgeries, that could be on a lifetime of suppressive antibiotic therapy, they could also lose their limb, we have to do better. What surgeons are trying to do is they're trying to create high localized levels and retention of antibiotics over prolonged periods of time. vancomycin is the go to antibiotic for this. It's very good against MRSA infections, and also very good against Bone and Joint infections. But it does require four weeks of prolonged exposure onto a biofilm to overcome it. That's because it is a time dependent antibiotic, not a dose dependent antibiotic. So you want a nice continued dose, the very best product that surgeons have today to try to achieve that is shown in the red. You can see that after a week and a half. Effectively, it's got nothing left to give with a massive drug burst on day 160 5% coming out. Contrast that to cognitive loss gel, our product, the absence of drug bursts, nice controlled extended release, I'm showing how through six weeks, but it actually runs out to about 10 weeks worth of data. So that's exactly how vancomycin likes to be delivered to overcome the challenge of biofilm infections. And I think this product has the potential to revolutionize an entire industry. So lots of really exciting things happening at locate over the next few months. Getting really excited about starting our human clinical study on our next generation BMP two products. We will be starting a series B later this year. So if anyone would like to talk about the products, the underlying science behind the products are what our series B looks like. Please do grab me in one of the breaks. I hope you found that interesting. Thank you for your attention.