Hello everyone, thank you so much for joining today to hear about Sernova and a future where chronic conditions are no longer insurmountable obstacles. I just want to start by thanking Suraj and the Oppenheimer team for welcoming Chris Barnes and I to talk today, and for moderating our session. To everyone joining in and listening, thank you so much. I hope that you enjoy our discussion today and ask questions. We will be posting this presentation on our website, so you will be able to go to www.sernova.com and review the slides in case I go through them too quickly. Disclaimers and forward-looking statements: you are all probably very familiar with this, so I won't linger. Sernova, who are we and how are we aiming to change the world? I consider us as trailblazers in the regenerative medicine space.
We are a clinical-stage company, pre-revenue. We have one asset in the clinic, so we have a phase I/II study for Type 1 diabetes. We also have additional programs in the preclinical exploration space, including postoperative hypothyroidism and for hemophilia A. We are in possession of the Cell Pouch System, which is a proprietary technology. It is our delivery vehicle. So we use the Cell Pouch, which is a credit card-sized device. It is made of polypropylene mesh sheets of material with perfectly sized pores. Those pores become vascularized after we implant it into the body of the patient. We then go in afterwards and add our therapeutic payload into the Cell Pouch. And at that point in time, the Cell Pouch functions as a pseudo organ, and the body can then go on to do what it wasn't biologically capable of previously.
This is how we say we are bringing functional cures for chronic diseases to patients around the world. It is important to note that we are an ethically derived therapeutic cell source, so today we are in the clinic with human donor islets. We'll talk a little bit about that in just a few minutes. In the future, we are going to be in the clinic with induced pluripotent stem cells. We are working on that with our partner Evotec. I'd like to share with you the statement from our first patient in our phase I/II study that's in the clinic now. This patient is insulin-independent, and she has been for just about four years.
So if you think about what Type 1 diabetes is like to manage as a patient and for the families, after I read the statement to you, you'll be astounded with what I'm sharing. So the patient goes on to say, "After completing the safety, tolerability, and efficacy study of Sernova Cell Pouch for clinical islet transplantation, and as the first transplant candidate, I can easily state how absolutely wonderful life is to be free of always thinking of how to manage my diabetes. After having Type 1 diabetes for 47 years with approximately 21,500 injections of various cow, pig, synthetic insulins, 34,000+ fingersticks, 1,500 urine tests, 15 years on the pump, carb counting, blood tests, low blood sugar reactions, and doctors, doctors, and more doctors' visits, I have now been free of the need for injectable insulin for 15 months." So this statement was from June of 2021.
This patient is now at just about four years insulin independence. So that means that she has not had exogenous insulin shots, which is amazing. We use the words transformational or life-changing a lot in the life sciences industry, and I feel that it's very applicable for the treatment and the functional cure that we have at Sernova. So let's talk at a really high level. What do we do at Sernova, and how are we expanding the work that we're doing? So we have the Cell Pouch System, which I talked briefly about a moment ago. It forms essentially a pseudo organ, and that pseudo organ is capable of administering cell-based therapy. So cell therapy, tissues, proteins, hormones, blood factors, it ensures complete containment of the therapeutic payload and full retrievability.
This is really important because what we're hearing from partners, collaborators in the industry, regulators around the world is that it's increasingly important to them, regulators, that is, that the therapeutic payload that is delivered to patients, so whether it's cells, gene-edited cells, xenogenic cells, that that therapeutic payload can be retrieved if anything were to go wrong with those cells that were placed in the body of a patient. And we're able to do that. I'll show you a few pieces of evidence in a few minutes. We have established a very nice proof of concept in patients with Type 1 diabetes, so we've borne out the concept that the Cell Pouch with therapeutic cells works. We have preclinical proof of concept established in hypothyroidism and HemA.
In our Type 1 diabetes ongoing study right now, in our first cohort of patients—that has six patients in it—five of those six patients have achieved insulin independence. They've also achieved other clinically meaningful benefits, including a reduction so that their HbA1c numbers are back down into the prediabetic or nondiabetic range, and then they also have circulating C-peptide levels, which is nice to see as well. We are then moving on to an iPSC-derived islet-like cluster study in collaboration with Evotec. We have IND and CTA enabling activities being conducted across this year. We have had some positive pre-submission regulatory interactions to date. That study will start in 2025. We also do have our Hem A and hypothyroidism programs in preclinical exploration. I'll talk a little bit about both in a few moments. So I'd like to share with you a few new developments at Sernova.
So it's always good to share something new in conjunction with talking about the great work that's going on. So across this first quarter of this year and very recently, in fact, our histology team in London, Ontario, has shown some evidence that we have long-term islet survival in the Cell Pouch. So this is from our phase I/II Type 1 diabetes clinical setting. And what histology is showing is that we have evidence of abundant vascularized islets expressing insulin throughout the Cell Pouch chambers in a patient from our Cohort 2 study or Cohort 2 of the Type 1 diabetes study. So this is a patient who has had the cells transplanted for over a year. This patient has sustained elevated C-peptide levels and also has achieved insulin independence.
So you look at that, and we get asked this question quite often, like, "How long do the islets survive?" We haven't been able to answer that question until now, until today. We believe this to be a first in the industry, and that is proof of demonstrated long-term islet survival in the body. So it's really exciting for us because it's another proof of concept that this concept of the Cell Pouch and therapeutic cells really does work. I'm also excited that we are able to announce a new research program with our partners, AstraZeneca. So as you might know or might have read in the past, we do have—we have had in the past some research collaborations on specific projects with AstraZeneca, and so we are expanding our work with the AZ team, and that's very positive for us in a new research collaboration.
So another exciting development is that we do intend to file an investigational new drug application, IND, for postoperative hypothyroidism. So we have confidence that all of our preclinical work, including very recent, within the past couple of weeks, recent preclinical data in a large animal model is supportive of this IND filing. We will continue to move forward with our interactions with regulatory agencies in prep for this IND filing at the end of this year. We would then aim to start a clinical study in 2025. Another piece of information that you'll find really interesting that we haven't really talked about in the past, and I don't know exactly why, because it's another proof of the Cell Pouch power in containing and the ability to retrieve the Cell Pouch and its payload. So in conjunction with a partner, there was a malignant cell study undertaken.
So this was an effort where we put malignant cells into a Cell Pouch and then put it into an animal. What you'll be interested to hear is that there was no evidence of any malignancy in the animal outside of that Cell Pouch. When the Cell Pouch was retrieved, no evidence of malignancy in the animal, which is really quite astounding, in my opinion. Again, this is something that we haven't heard of previously in the industry. So I'm putting another checkbox next to the Cell Pouch and what that device, what that delivery vehicle is able to do. We've also taken a lot of learnings from our Cohort 1 and Cohort 2 of our ongoing phase I/II study using human donor islets for Type 1 diabetes. All of those learnings are going to be applied to support our upcoming iPSC trial in 2025.
So what have we learned? Specifically in Cohort 1, learned a lot about the optimal dose and the optimal density for our cells. And then what we're continuing to learn across Cohort 2 is what is the optimal immunosuppressive regimen? So we've tested out a variety of advanced immunosuppressive regimens in prep for our iPSC study, and we think that we've gotten to the point where we know now what that optimal immunosuppressive regimen will be. And then really, the foundation of all of these new developments is that we do have the largest clinical database for Type 1 diabetes cell therapy. And when you look at how many patients we have in the clinic and the length of years that they have been in the clinic, we have a wealth of data that's really exciting for us and for our patients in the industry.
So all of those things that I just mentioned a moment ago, what you can see is it's overlaid on a timeline here. So starting with 2024 on the left, 2026 on the far right, I've put on this timeline where we will achieve various milestones. So on the top, we've got our asset-based milestones. On the bottom, which I haven't talked about, is some of our corporate milestones. So we do have a newer Chief Business Officer, Modestus Obochi. So Modi and I joined Sernova at about the same time in very early September. So Modi's been really busy in looking at what potential in-licensing or out-licensing opportunities will we have, what collaboration opportunities will we have. We have a fully functional virtual data room that is in existence now, so that's a new development or a newer development for the company.
Modi's been very busy in talking with potential partners across the industry. Looking at our pipeline, what you can see are clinical asset at the top and our two preclinical programs at the bottom. You see that for the human donor islet cell, phase III and the BLA submission are blacked out. This is because we do not intend to commercialize the human donor islet cell pathway or treatment simply because there aren't enough cadaver cells, essentially, in the world to treat the patients who we want to treat. Hence, going forward with the iPSC islet-like cluster study, because then we can treat millions of patients around the world and impact as many people as we possibly can. What we've also done is to think about what is our portfolio strategy. Beyond Type 1 diabetes, beyond hypothyroidism, beyond hemophilia A, where else can we go?
And so the team at Sernova has done a pretty detailed assessment over the past few months, and we've identified a number of other chronic disease areas for further exploration and pipeline expansion. And we feel like we have a nice focus on endocrine disorders. More to come on this news as well over the coming months and specifically what indications we would like to take a look at. So a little bit about the Cell Pouch and how it works. So on the left-hand side of this slide, what you'll see is a pictorial of what the Cell Pouch looks like in the body. We place the Cell Pouch in the body of the patient, allow it to vascularize, so to create that really healthy and optimal environment for cells to be then transferred into after a couple of weeks of vascularization.
After the therapeutic cells or tissues have been in the patient for an additional few weeks, what we do in the case of Type 1 diabetes, we begin to titrate the patient off of insulin, and the Cell Pouch and the therapeutic cells begin to then do the work that the pancreas was intended to do, but just isn't able to in Type 1 diabetes patients. And so at that point, the patient has been titrated down on their insulin and becomes, in our case, insulin independent after a number of weeks or months. We're also working on the development of a toolkit, and so that toolkit will allow for that consistent pouch placement in therapeutic payload transplantation. So that toolkit is underway right now. We feel like that's going to be an important tool to ensure that consistency across various different locations in the world.
Let's talk a little bit at a really high level about the approach that we're taking: Cell Pouch plus donor islets. We're in the clinic today. In the future, we will be going into the clinic with Cell Pouch and i PSC studies. We have a number of animal studies that have been conducted already, and we will be doing additional preclinical animal studies coming up across this year. In those preclinical animals that we've studied thus far, what we've been able to show is that there is a functional equivalency, essentially, between human donor islets and those Evotec-produced i PSC islet-like clusters, which really bodes very well for our next study, our phase I/II study with i PSC cells, because we expect to see similarly, or we're hoping to see similarly positive clinical data. Large market for Type 1 diabetes, right?
So we've got a number of patients in the U.S., so over 1.5 million Type 1 diabetes patients in the U.S. When you broaden that out to the world, you're looking at probably a total of 8-9 million Type 1 diabetes patients. The Cell Pouch with islets, it can also help treat Type 2 diabetes patients who are insulin dependent, and that population is about 30% of the Type 2 diabetes market. So this is a very appealing market potential for us and then for patients around the world. I think I'll skip this slide mainly. What I will say is that the approach we're taking with islet therapy and the Cell Pouch is a far more holistic way of treating patients than what the standard of care has been over the past 100+ years, and that's basically insulin.
The approach we're taking is a holistic approach, and it targets alpha, beta, and the delta cell portions of the islets that are in the bodies of healthy patients and that we aim to reproduce and which we are reproducing in our therapies that we're in the clinic with today. High-level overview of where we are from a clinical trial point of view. So primary endpoints, safety and tolerability. Secondary endpoints, there were multiple of them. Survival of the islets in the Cell Pouch was a critical one, and I'll show you a visual of those surviving islets in just a few minutes. We wanted to see a reduction in hypoglycemic events, which we did see. We wanted to see HbA1c reductions down into the non-diabetic range, and then we also wanted to see that circulating C-peptide, which we have seen.
What we didn't have as an endpoint, but which we have achieved in a number of patients, is insulin independence. On the left-hand side of the slide, what you'll see is our immunosuppressive regimen at the bottom. Cohort 1 included tacrolimus, MMF, and abatacept. What we decided to do in Cohort 2 is to mix things up a little bit because MMF and tacrolimus are a little bit difficult from a patient perspective. So we dropped down the level of tacrolimus. We have added belatacept, and what we're also doing is looking at the levels of MMF as well. So more on this in the future. I will skip this slide in the interest of time because I'm just looking, and I've only got a few more minutes before we come to questions. I will show you this slide.
So this is our HbA1c levels for patients in the Cohort 1. So in the light blue is post-transplant, and what you'll see is that those levels have come down rather nicely. The dark blue was when patients were on their optimal insulin therapy before going on to the Cell Pouch plus the therapeutic cells. So all six patients in that first cohort have achieved HbA1c values in the non-diabetic range, which is very, very appealing and very exciting for us. I'd like to show you a little bit of data on the Evotec-produced, so engineered and produced iPSC islet-like clusters, just so you can get a feel for how similar they are to the human donor islets that we're using. So what I will show you is a graph that actually overlays both or that shows us both.
So on the left-hand side of or on the right-hand side of the screen, top bar graphs that you see, in the blue is the Cell Pouch with those islet-like clusters that have been engineered and produced. On the right upper side of that slide, you see the human donor islet cells. And what you can see is that those numbers, the C-peptide levels, they are essentially exactly the same. So that's a positive thing because it tells you that Evotec has done a really good job in designing exactly the right proportion of those alpha, beta, and delta cells. This is further reinforced when we drop down to the bottom of this slide on the right-hand side and look at the oral glucose tolerance test. You see those two lines, so blue with the Cell Pouch and the islet-like clusters, black for the human donor islets.
They essentially say the same thing. So, after a bolus of blood glucose is given to the animal, the blood levels then go back to normal after about 45-90 minutes. You see them nicely decreasing. This is an overview of our histology results. What you see is surviving islets in both the alpha, beta, and delta cells. So the green is a nice vascularization that's visible on the CD31 marker, and that's throughout the ILC graft in the Cell Pouch. And I think I will stop there and let Suraj lead us in a few questions. Again, this presentation will be on our website. I'm sorry that I didn't have a chance to go into some of the details of data that we've seen with our additional pipeline, but please rest assured that we'll share this on the website. Suraj?
So yeah. Cynthia, can you hear me all right?
I can hear you well. Thank you.
Perfect. So Cynthia, just let me ask the questions that have come in the chat box, and then I'll have my own questions. So start with the last one first, which says, "Why was the last patient in Cohort 1 not able to achieve insulin independence?
So the last patient in Cohort 1 came in a little bit later than the other patients, and so that was one of the reasons why we don't have additional data on that patient yet. But also, there were some challenges, is probably the best way to put it, with the immunosuppressive regimen. And so the patient had dropped some of those immunosuppressive drugs, so that made it a little bit challenging to then reach that insulin independence time point or data point.
Got it. Got it. Second question, "Were the malignant cells able to survive in the pouch? How long were they in there for?
That was, I don't have all the details at hand. It was at least, I would say, 30 days, and there was evidence that the malignant cells were still alive in the Cell Pouch, but they were not existing in the mouse.
Got it. Got it. So Cynthia, if I got the one of the interesting things, the points you made, and please correct me if I got it wrong, it seems like the Cell Pouch was active for over a year, right? That's one of the things that you'll have said, or did I get that time point wrong?
Nope. So I can clarify that a little bit. So the Cell Pouch that I mentioned where we saw abundant, I'm just going back to that slide so that we can see it. So I think it was the top bullet on here, Suraj. So what we were able to do is to excise one of our Sentinel devices from the patients, one of the patients who had been in Cohort 2 for over a year. And we were able to see that abundant vascularized, so living islets. They were thriving. And that's the first time we've seen evidence of those really nicely surviving islets because typically what we had done in the past is we would take a Sentinel device out, and those are just mini Cell Pouches. So we would take those out at about 90 days and verify that, yes, the islets are surviving.
And so that's why, if you recall the slide where I had the secondary endpoints, and one of those secondary endpoints was survival of the islets, we would demonstrate that at 90 days. We didn't have a long-term demonstration or proof that those islets were still surviving. We surmised that they survived just based on the clinical results we were seeing. Now we have that proof. So we have the proof that can say those islets have survived for over a year from the date of transplant.
So Cynthia, in terms of do we know specifically what percent of the cells have survived and are functional enough to produce a threshold insulin level? And also, can we make any correlations or extrapolations for how things would work with Evotec's iPSCs?
Yeah. So I'm glad you asked that question, and I asked our clinical lead, Frank Shannon, just the other day that question because it's a very valid question. So what Frank told me is that well over 90%, probably closer to 95%-97% of those cells were living, which is really exciting because I think in some other studies that might have been done in the past, not by Sernova but other colleagues in the industry, there was only maybe a 3%-7% survival of those islets. So for us to see the vast majority of those cells still surviving is really exciting to us.
And then I think you asked, "How can we extrapolate that to the iPSC trial?" So because we have that animal data comparing the Cell Pouch with human donor islet cells versus the Cell Pouch with those engineered and produced iPSC islet-like clusters from Evotec, because we have that data, and essentially they're showing functional equivalency, and we know that the human donor islets work really nicely in the Cell Pouch in treating patients, we have a very high degree of confidence that that can be extrapolated to the iPSC islet-like clusters. So we're very much looking forward to getting in the clinic with those iPSC cells and seeing positive patient outcomes.
Cynthia, remind us, it wasn't obvious to me, iPSCs, when will the phase I/II in 2025 you're slated to begin iPSC trials?
Yes. Can I clarify something that I said a moment ago? So my team here, Modi and Frank, and Chris has kindly corrected me that the malignant cells were alive in the Cell Pouch, and the test was for 90 days. So it was more than I said, 30 days. So I just want to clarify that. So that's better news because the survival in the Cell Pouch of those malignant cells was longer, and then they were actually in the body of the mouse for longer, and they still didn't have any sort of issues with infecting the mouse. So your next question, Suraj, was about the i PSC trial starting in 2025. Is that correct?
Correct.
Yeah. So what we're doing with Evotec right now is a number of continuing process development aspects of work. We're scaling up our manufacturing. So our process is due to be locked any day, which for any of us who have been in the manufacturing and process development world, this is really exciting. We are starting our preclinical studies with Evotec in the coming weeks, I believe. So we're sending Cell Pouches to Evotec now to support those animal studies. And all of that is in support, of course, of filing the IND. We're planning to go into a number of sites. So whereas our study right now in Type 1 diabetes is at one center, and that's the University of Chicago with Dr. Piotr Witkowski, we will be going into several sites. So we would like for one site to be in Europe and a few in North America.
We have also had positive initial regulatory interactions. So that study, iPSC study, is anticipated to start at the end of 2025. Of course, Evotec and Sernova teams are working very hard to try to accelerate that timeline, but right now we're sticking with the end of 2025, fourth quarter.
Got it. Cynthia, we just have about a little over a minute remaining. So Cell Pouch pricing, $200,000-$400,000, for what duration? I guess that's a question. And also quickly, any thoughts in terms of GLP-1s, any additive relationship to Cell Pouch?
Yeah. So I think you're referring, Suraj, to the slide that talks about the market potential. So what we did was a payer study a couple of years ago, and I do feel that that payer study or that payer support that the initial study indicated between $200,000-$400,000 per patient is what insurers would be willing to pay. That is going to be higher now, I'm convinced, because we have much longer duration of those clinically meaningful results, including insulin independence and the other outcomes that we wanted to see.
So this is really what the payers said that they would pay based on when you think about the burden of care of what it takes to keep a Type 1 diabetes patient healthy, and when you think about the outcomes or the challenges that they might have in their lifetime, so cardiovascular events, kidney issues, loss of limb, loss of vision, and potentially even loss of life. So it's a very serious disease. And when we can bring those or when we can bring those far down or eliminate them, and is what our hope is, then insurers won't be paying for cardiovascular issues and such. So that is our initial potential pricing. Might change along the way. And your other question, Suraj, if you can remind me, was.
GLP-1s?
GLP-1s. Yep. Yep. So there's been a lot out in the industry about the GLP-1s. It's a huge boom for the industry, and it's a win for patients too. What the safety will look like in years and years, I'm not certain. We are thinking about, is there any applicability for us in GLP-1s, but we don't really see it for the Cell Pouch and the work that we're doing today. We think that the approach that we have is a little bit different and also very meaningful for the patients, the diabetes patients.
Got it. Cynthia, we're up on time. Fascinating story. You guys are doing something very unique, and I wish you all the best and hope to see you soon.
Thank you. Yeah. Thanks, Suraj. Hello to everyone from London, Ontario. The team says hello to everybody. We're small but mighty. Thank you for listening. We appreciate you.