John Swart, Cytotheryx - Increasing the Supply of Liver Cells | LSI USA '24

John Swart  0:05  
Well thank you for coming and really appreciate the opportunity. The pleasure really, to introduce psychotherapy, psychotherapy as a spin out of the Mayo Clinic focused on the production of primary human hepatocytes and the use of those for liver disease. As you may be aware, liver failure is the 12th leading cause of death in the United States, and there is no treatment. Very, very few treatment options at least and certainly no cure. With the production of primary human hepatocytes, we believe that we can change that. So primary human hepatocytes have been shown to be an effective treatment for liver disease, but there simply is no source. And so the only source today of primary human hepatocytes is actually organ donation, and only those livers that are not healthy enough for liver transplant. And so that limits that availability significantly where the entire global market is restricted to about 10 kilograms of material. That material today is used for toxicology testing. And so we show that here on the research side, that's required by the FDA that chemicals are test tested for toxicology 80% of that market. So that takes up all the available cells. But with the ability that we have brought with our platform technology, we believe that we can produce kilogram quantities of this, this important cell type and be able to address a significant therapeutic need. We produce those cells in what we call a bio incubator. And so just like current sources of primary human hepatocytes, we take in donor livers. We then isolate the primary hepatocytes from those livers. We freeze those down into a master seed bank, we test those cells to make sure that they're healthy and safe. Once we have a master seed material identified, we pass it through our bio incubator, we see about 1000 fold expansion of those cells, we re isolate those cells away from the bio incubator, and then we use those cells for a number of different opportunities. So what is that bio incubator? Now bio incubator is actually a genetically engineered animal. So unlike any other organ in the body, the liver has the ability to regenerate. And so understanding that capability. over 20 years ago, a group of researchers introduced three different genetic changes manipulations to mice that would predispose them to liver failure on their own, but also allow for human cells to implant and expand within the mouse's own liver, and they showed that to be very effective 90% humanization of the mouse's liver within a weeks, that technology was then transferred to a rat. That rat showed similar opportunities. But the problem with rodents is their livers relatively small. A mouse has a one gram liver a, Arad has a 10 gram liver. And so when you're starting to look at the need for 10s of kilograms, or even 1000s of kilograms of material, you need a different bio incubator and so psychotherapy is brought to the market and FRG pig. A pig has at six months of age about a 1500 gram liver, which gives us the ability to produce kilogram quantities which should be 10 to 30 doses of human material per bio incubator. So with that ability to produce those cells, we really see three different significant opportunities to apply those cells. There is this research opportunity, which is the current market. I want to talk about each one of these individually just at length. So there's a research opportunity. There's actually an artificial liver a biologic artificial liver device opportunity, and a direct cell transplant opportunity that could replace whole organ transplant. on the research side, this is a $240 million market, currently supplied by cells primary cells isolated from discarded livers. The FDA drives this process 80% of that market is for toxicology testing, by large therapeutic companies. So the total market size $240 million. The question that we get is will the cells even though you've created a master seed, you've passed it through the bio incubator. Will these cells behave like primary human hepatocytes after being passed through the bio incubator? And the answer is? Absolutely, they will so three functional tests that we perform on the cells, human albumin production, sip three, a four activity, as well as ammonia detoxification important functions of primary hepatocytes. And not only do we see this continue to function in that way, we actually see slight improvement, and so you can understand why that might We are harvesting the cells in a very controlled environment versus livers that are taken from organ donation. So while that's a very attractive business 95 plus percent margins with a $240 million global market, really the big opportunities are on the therapeutic side. And so we also have patents around a liver an artificial liver device, a biologic artificial liver device, that device could be used to keep someone in who is in liver failure alive, while their own liver regenerates or long enough to find a better match. In the liver transplant process. We put this technology in a sub subsidiary company that we call Ponce de Biosciences. And it's a huge market 150,000 People in liver failure in the ICU in the United States, every year 10,000 of those people will receive a liver transplant 50,000 of those people will die with no other options. This device, if you hooked them up to this device will function as an external liver, it'll keep that person alive, functioning as if their own liver is functioning, while their own liver either regenerates or giving them more time for transplant. And so we're really excited to move this forward. The Mayo Clinic develop this device tested it in large animal models to show that it worked very effectively in pigs, non human primates and dogs, we are currently making a GMP grade device to move the project forward into human clinical trials. And then the third application is a cell transplant. And so while there's limited organs available for transplant, the cells themselves could be used instead of whole organs. And so we are taking the cells directly into patients. But really, we focus this initially on the rare disease space. And so while this should work for people in liver failure, it's a great opportunity to go after the rare disease space because a child born with hemophilia type B, or PKU or hereditary tyrosinemia type one, if you gave them a transplant, you would cure them. But we can give them a bolus of cells 10 to 20 grams of cells at birth, and that if we can get to 10% of the population of their cells, being ourselves we'll have a durable cure for that patient for life. And so we're gonna go after a rare disease indication initially with the idea that we'll have follow on indications in the larger market. So where are we at in this process? And so on the research side, we intend to have product ready for commercialization next year already. So we intend to enter the market with primary hepatocytes for toxicology testing in mid 2025. In the liver assist space, we're looking at finishing up our preclinical activities, we're currently building out a GMP grade device, we'll need to run one additional animal efficacy study and one dog safety study. Before we can go to Phase One, two trials. And then on the cell direct cell transplant space we're working on transferring this technology to our bio incubator will then finish up that preclinical space and we'll be looking to phase one to sometime in 2027 or 2028. We have the team to move it forward. So we have a scientific advisory board that's world renowned. Dr. Marcus grumping is kind of the godfather of this technology. He's been working in this space for over 20 years. We have other advisors that are known globally. And then we've got the team who's here today with me, and Argo who is our Chief Business Officer, Dr. Ryan Scholes, who is our our chief scientific officer. We have a booth downstairs. We'd be happy to answer your questions as we get there. What are we looking for today we're we're looking to raise a Series A so we've raised about $20 million thus far. To get us where we are today. We're going to raise a $45 million series A this year with the idea that that should provide us the resources we need to build out a lab, finish up our preclinical work and then do our Phase One two trials. I appreciate your time we'd be happy to talk to you downstairs in the Pacific ballroom at our booth if you're interested in learning more. Thank you very much