Gloria Matthews, Ankasa Regenerative Technologies - Novel Regenerative Medicine | LSI USA '24

Gloria Matthews  0:04  
Good afternoon, everyone. I am Gloria Matthews of Ankasa regenerative therapeutics and I'm actually here to talk to you about something that you might be surprised to see at a med tech conference. This is a bill a pathway, local liposomal WINNT protein for endogenous stem cell modulation. And the reason for that is that not only is it a rigorously studied therapeutic, but it has the potential to address a huge market in the in the med tech space. This company was co founded in 2015 by Sandy Madigan, Avalon bio ventures who's has decades of transactional experience. And by Gil helms at Stanford who has spent over 20 years researching this protein this pathway, I joined in 2019. And I bring the strong clinical background, regulatory background industry background as well as deep r&d networks. We got an $18 million series A in 2015. We've gotten $6.1 million in service award funding and $12 million series A extensions in 2024 clinical development when we opened our ind, we have just enrolled that finished enrolling at the end of November of last year, our phase one to be study and we're ready for pivotal stage. So why wouldn't proteins so these are anytime you have an injury or disease in tissues, he needs stem cells and stem cells have to be told what to do in order to get the right type of tissue, whether it's nerve tissue, lung tissue, eye tissue or bone. Because they're so important in the body, they have to be regulated very carefully. So when proteins have to be protected from aqueous environments in order to remain stable in the body, this makes them very hard to produce and purify. And Akasa has developed proprietary methods to GMP manufacture and stabilize went through a for clinical use by inserting the hydrophobic piece into the hydrophobic portion of liposomes. And leaving the ligation portion out exposed in the environment, so it can target its receptor. So rt 352 l that is went through a protein inserted into liposomal membranes. We have broad coverage of five patent families for this, this therapeutic over 40 US and international patents issued with multiple pending, we have an aggressive IP strategy and portfolio currently has no obligations or restrictions. So you can imagine then that this because it's a stem cell modulator could have pretty significant platform potential. We, however, are not focusing on a platform at this time, we are focusing strictly on bone and more specifically on spinal fusion, hence med tech conference. We know from our studies, as well as many studies across the globe over the last decade that went through a is a powerful bone forma, we know that it activates bone forming osteoblastic pathways, we know eight inhibits bone resorbing osteoclastic pathways, and we know that it drives osteogenic gene expression. But importantly, local delivery of this wind protein can be accomplished by taking bone autograph, soaking it in the protein solution, it just looks like an aqueous solution. And then putting it back into the body as you would for most orthopedic surgeries. This allows you to keep bone from it exactly where it's meant to be. I know this is busy, so bear with me. Here's why. Because these naturally in the body, there are receptors for when three a they have funny names like frizzled and LRP, five, six. And if you take the up on the with the rabbit picture, if you take bone graph, and you soak it in the protein or you have a control that has no bone graft in it, you get and then you look at what happens to the the activity in the in the solution, you find that it the blue line at the top of the far right upper graph that nothing happens that the activity stays at 100% over 90 minutes. Whereas if you have bone graft the yellow line, you see that it disappears from solution and the reason it's doing that is it's been taken up by the bone graft cells. And we know that because in the lower right panel is a sample of some of the panel of osteogenic genes that we know this protein can then induce. It's very simple to put in in the or it does not add surgery time it doesn't add complexity. So harvest of bone autograft is standard for most orthopedic procedures involving bone. So bone graft is harvested, it's milled in the Stryker bone mill which both wheat and Stryker have data to keep the cells of the bone graft viable, which is important for gene expression. It's measured for dosing bases, and then it's soaked for 30 minutes while the hardware has been implanted and other things are being done in the surgery. And the time it's needed back it can stay there longer. And when it's needed back, it's replaced back in the body per standard of care by the surgeon. This is a huge market. We have focused on spine fusion based on a market analysis that we did back in 2020. Showing that the lowest hanging fruit for us was spinal fusion. We our market opportunity at that time was about $3.7 billion. The interesting thing about this is even though it's the tough PLA path, the PLA path toughness comes from tackling GMP manufacture getting your GLP toxin, making sure you get into ind taking care of your ass A release specifications and assay qualification and getting into first inhuman patients. All of that has been done. So this is considerably de risked and the value, one value of having a belay pathway, even though it takes a bit longer is that if you get one with, for example, spinal fusion, there's so much rigorous data backing this up both preclinical and clinically, that getting these other pieces bolted on is a lot easier than it is trying to get each of them to novo. The other facet to that is that the uptake clinically is much better and also by reimbursement. A one thing I want to point out on that was a segment reimbursement. So if you look down there, these these market opportunities, consider the price of the product to be settled between one and $5,000. This is similar in concept to Medtronic infused retirement human BMP two which is put on a college and sponge and put into the spinal fusion area. This is the price point that they are currently getting. And they have reimbursement for this. Interesting the cost of goods for this, to manufacture is about 100 bucks. So the margins here are huge. We know from our studies and our labs, both at Stanford and on Casa that this is this product is very efficacious in bone formation and all these models that you see here, just put some schematics that are some pictures just to give you an idea. On the left in each of these pictures is the art 352 l treated and in the right is representative of the PBS there will saline control treated and I think you can see that there's a lot of bone, no bone, good bad purple bloob. The it's clear that there are quite good efficacy signals. Those are all published as well. And I'm happy to provide publications to anyone who would like them. We also know from our models, both in aged rats and young rabbits that we have efficacy in these fusion models. So as early as day 49. In the upper panels, you can see that the bone graft plus the wind drives much higher new bone versus initial bone formation and in the young rabbits who probably don't need went through a to heal anyway, we see a dose dependent increase in the number of sites or the percentage of sites views at 12 weeks. We embarked on a phase one B to A evaluation of this product in posterolateral spinal fusion so we could single level posterolateral fusion with a tiller for transforaminal, lumbar interbody fusion for spinal listhesis spondylosis or stenosis. Only the posterolateral fusion site is treated with rt 352 l and we assess it to an eight weeks 612 and 24 months for a CT fusion by CT radiography for safety mostly patient reported outcomes for pain and fusion. And we had a robust data set with central radiology reads with two primary readers, and one adjudicator. And as I said that enroll was completed November 2023. And as COVID would have it, we have kind of a subset that initially enrolled and then we have some later so we actually have one, almost two year data on that early subset. And we're just getting the one year data on that last subset. We've had quite a bit of interaction with the FDA and don't need to go through all of this, but we have comparability protocols established that that they have accepted amongst all the lots that we've used for talks for this study. And for the next study. We also have agreement on the design of the sheep GLP toxin dose range finding study needed for the next study, and we have agreement on the face to be pivotal study. Our GMP manufacturing has been scalable, up to 200 liters scale and you need to go through all these we have over 600 miles from the current clinical study over 3000 vials from the new process which is more potent and higher concentration. And we have as I said comparability we have stability out to five years. This is the part that that people cringe at when they're in the med tech world. This does take time and we expect to be at DLA by 2029. The good thing is that most of the hard work has been done and once we get through that a smaller investment now works out to be a much bigger investment later. So I think it's worth the wait. Finally, we're asking for a $35 million Series B we have the potential of a certain grant and right now for $15 million. If we get a $10 million co fund they will be very enthusiastic about that grant. We that will allow us to complete the phase two B and initiate three do the VLA preparation and GMP manufacturing that we need to do to get the phase three drug product. We can potentially initiate studies and other areas of that was of interest and do clinical in use optimization research. Thank you for your time.