Morning everyone, and welcome to the 27th annual H.C. Wainwright Global Investor Conference. My name is Joey Breska, and I'm an Equity Research Associate at H.C. Wainwright. It's my pleasure to introduce Nikki Keith of Sana Biotechnology.
Hi, I'm Nikki Keith, Vice President of Finance at Sana Biotechnology. Thanks to H.C. Wainwright for the invitation to present a business overview at today's conference. I will be making forward-looking statements during the presentation. Please refer to our latest 10-Q, including the risk factors. Sana aims to change the possible for patients by developing engineered cells as medicines. Today, I will discuss our two foundational platforms: one for overcoming allogeneic rejection of cells, the HypoImmune Platform, and another platform for cell-specific in vivo delivery, the Fusogen Platform. Today, I will mostly focus on type 1 diabetes, but we'll also discuss our allogeneic CAR-T and in vivo CAR-T programs. Here's a view of our pipeline, and we'll review the latest six-month data from UP-421, a HypoImmune-modified primary islet cell therapy.
We will also touch on SC291, a HypoImmune-modified CD19-directed allogeneic CAR-T for B-cell-mediated autoimmune diseases, SC262, a HypoImmune-modified CD22-directed allogeneic CAR-T for blood cancers, and SG299, an in vivo CD19-directed CAR-T for B-cell-related diseases. Let's talk about the problem we aim to address. Since the advent of transplant medicine, the rejection of allogeneic cells has limited the broad implementation of cell therapy. If I give my cells to you, you will recognize them as foreign and kill them. To date, the industry has approached the problem in one of two ways. One is profound immunosuppression, so that the immune system has no ability to find the cells. The other way is to use autologous or your own cells. Both have challenges with the ability to scale. On the right-hand side of the slide, we have a schematic of Sana's HypoImmune approach.
There are two arms to the immune system: the adaptive and the innate immune system. The adaptive immune system is mostly comprised of B and T cells, and we deal with the adaptive immune system by disrupting MHC class I and MHC class II. There's also the innate immune system, mostly comprised of your natural killer cells and macrophages. When the innate immune system detects the removal of MHC class I and MHC class II, they kill these cells. Sana's real insight has been to overexpress CD47. By completing these three edits: knocking out MHC class I and class II, and overexpressing CD47, you will turn off both the adaptive and innate immune system, and the result is true immune evasion. We're going to walk through the clinical data in type 1 diabetes next, but I wanted to show that this work has been published repeatedly.
Most recently, the clinical data in the human proof of concept type 1 diabetes study in The New England Journal of Medicine. The print version was actually released last week, which includes an editorial that reviews the mechanism of the HypoImmune Platform. Let's discuss type 1 diabetes. Type 1 diabetes is caused by autoimmune destruction of insulin-producing beta cells, resulting in no insulin production. It's a large unmet need with approximately 9 million people with the disease, and it's growing. If you have this disease, even with the best possible care, you live about 10 to 20 years less than someone without the disease. During that time, with too high of blood sugar, you have the risk of amputations, blindness, heart attack, stroke, and kidney failure. With too low of blood sugar, there is a risk of coma and/or death.
This disease, there hasn't been a meaningful change in the standard of care in over 100 years. We believe we have a real opportunity to make a very important medicine. We know that advancing towards a cure for a broad type 1 diabetes population is possible due to these three items. As I just described, type 1 diabetes is a relatively simple disease to understand. It's the missing pancreatic beta cell, and the patient's immune system has killed the beta cell. I'm going to talk about islets. A pancreatic islet is simply a pancreatic alpha, beta, and delta cell. You can think of it as a pancreatic beta cell and its support structure. First, about 25 years ago, James Shapiro and others have shown that you can transplant cadaveric pancreatic islets, and they can be curative for a period of time for a patient with type 1 diabetes.
In fact, some people are out now 10 to 15 years with these cells. Unfortunately, the cadaveric islets aren't very scalable and replicable supply source, and the patients that receive these cadaveric islets have to be on lifelong transplant-level immunosuppression. There aren't that many people who would rather be on lifelong immunosuppression versus lifelong insulin. If you look at number two, you can see over the last few years, several different groups have shown that you can take pluripotent stem cells and make them into islets. That may be a more scalable and replicable source, but you still have the challenge of transplant-level immunosuppression. Third, and this is where Sana comes in, we showed that we can get rid of immunosuppression using the HypoImmune Platform. The results from our proof of concept study were recently published in The New England Journal of Medicine.
The critical data that we shared is that the HypoImmune Platform application in the clinical trial setting. We designed an investigator-sponsored trial with Uppsala University Hospital. The goal of the study was to take cadaveric islets, genetically modify them with the HypoImmune edits, and then transplant the cells into a type 1 diabetic patient with no immunosuppression. It's a procedure in which you inject the cells intramuscularly into the patient's forearm. The goal was to evaluate safety, immune evasion, cell survival, and C-peptide. As a reminder, this was a proof of concept study, so we were using a dose that's approximately 5% of what you would need to get true insulin dependence. If you look at this, we are pleased to show that we've met all primary and secondary endpoints of the study out to the latest readout of six months.
The patient is doing well and making his own insulin for the first time in over 30 years. There were no safety events from the study to date. We'll review some of the points from the study. The most important element of function is C-peptide. When a pancreatic beta cell makes insulin, it makes proinsulin and C-peptide. When it's secreted from the cell, it is cleaved into these two items. C-peptide is a direct one-to-one ratio of the amount of insulin a patient is producing. You can see that this patient at baseline had no C-peptide. As we follow the patient over the six months with the HypoImmune islets, you can see the stable C-peptide, and the patient is now making his own insulin.
Secondly, if you look on the right, we show the mixed meal tolerance, or MMTT, which looks at the patient's ability to respond to make insulin in response to a meal. You see the purple line at the bottom confirming that the patient had no insulin and no response in making insulin from a meal. What you see over the course of six months is that the patient increased C-peptide significantly with a meal as we repeat this test. We also took images. The first is an MRI. You're looking at a cross-section of the forearm of the left arm of the patient. If you take that yellow box and look on the right-hand side, you can see arrows. Those arrows highlight an area which is consistent with the cells. In this 12-week PET MRI, scanning also confirmed the islet cells at the transplant site.
Next, we'll review the immune evasion data. As a reminder, the patient, because of type 1 diabetes, had a pre-existing immune response to these cells, but the cells with the hip edits were not killed. The hip islets survived and functioned. For the IST, the cells come from a donor, and we make the HypoImmune edits. With different gene editing efficiencies, we don't edit 100% of the cells. Approximately 50% of the cells get all of the hip edits, but sometimes the cells have partial edits, like a double knockout of HLA-1 and 2 without the overexpression of CD47, or no edits at all as a wild type islet or unmodified islet cell. Now we take the product that we transplanted and test it against the blood of the patient to see what's happening inside the body. First, we're looking at the unmodified or wild type islet cells.
What you see is a very rapid T cell response to kill these cells, and then on the right-hand side, the antibody generation. These cells are gone. Next, we're looking at the double knockout cells. As you see on the left-hand side, T cells don't see them, and they don't make antibodies. What you see on the far right is that the natural killer cells, the innate immune system, are able to recognize them as foreign and kill them. Finally, our HypoImmune islet cells. What you see here is that throughout this time, the patient generates no T cells or antibodies that recognize these cells, and that natural killer cells are unable to recognize them as foreign and leave them alone. Here, we have a movie to demonstrate these concepts. In green, you see the cell types from the drug product.
You either see the wild type islets, then the double knockouts, and then the hip islets. When I start the movie, you can see that unmodified or partially modified cells are killed, and the hip islets are left alone. Now we have evidence in humans that we can overcome allogeneic rejection. At Sana, our goal is to develop a therapy that provides euglycemia without immunosuppression, SC451. It starts with a stem cell on the left that receives the hip edits and is differentiated into pancreatic islets. The goal is to manufacture at scale and deliver to the patient in their arm with a single injection. There are four distinct important scientific challenges, and we've made progress against these. The most challenging has been making a gene-modified pluripotent stem cell-based master cell bank.
This starts with a single cell where you make all of the gene modifications and grow the product from the cell that is stable over many, many passages over time. We've done this, and the next step is to complete the remaining items to file an IND. We expect to file an IND for SC451 as early as next year. That's our type 1 diabetes program. Next, I'll briefly review our allogeneic CAR-T programs in autoimmune diseases and blood cancer. We applied the HypoImmune Platform to make allogeneic CAR-Ts, and we have two programs in development. For autoimmune diseases, there are approximately 70 different indications where at some level there's evidence that depleting B cells or knocking down B cells has clinical impact. You can also see the depth of B cell depletion predicts efficacy in early trials.
In fact, we've shown B cell depletion data from our discontinued SC291 study in oncology, where SC291 is well tolerated and results in deep dose-dependent B cell depletion in oncology. The Glean trial is evaluating SC291, a HypoImmune-modified CD19-directed allogeneic CAR-T across SLE and AAV, and it's ongoing in the dose escalation phase 1 study. For oncology, there's an unmet need for patients that relapse post-CD19 CAR-T therapy. We use the same HypoImmune edits for SC262, a CD22-directed allogeneic CAR-T in CD19 CAR-T exposed patients with relapse and/or refractory NHL. The VIVID trial is ongoing in the dose escalation phase 1 study. We are enrolling patients in both of these studies and expect to share data in 2025. Let's briefly discuss the second platform, the Fusogen Platform. This is a cell-specific in vivo delivery system. We are leveraging insights from nature to deliver various payloads to specific cells without lymphodepletion.
We've been working on this platform with an in vivo CAR-T cell. The goal is to make a therapy off the shelf, and the technology is called a Fusogen. It has an F and a G component. The G is the guide, and the F is the fusion. We manipulate the guide so that we only recognize the cell of interest, and then that will drive fusion of the cell membranes. You get cell-specific delivery and the genetic content that goes directly to the cytoplasm. This is the general concept. Our medicine is on the left-hand side. It has a cell-specific delivery capability that will drive it just to go to T cells in the patient's body. It will then deliver the genetic content, which is that little minus sign. The genetic content will make a CAR, which is that yellow and blue Y.
The CAR will recognize B cells, and when it does, it will activate. An activated CAR-T cell will do two things. It will divide, and it will kill that target. Our lead product candidate is SG299, and it's a CD8 targeted fusosome that delivers CD8 T cells to the genetic material to make CD19-directed CAR-T cells. Earlier this year, we showed some NHP data demonstrating that SG299 surrogate with another component can lead to deep B cell depletion in non-human primates without the use of any lymphodepleting chemotherapy. This is also while avoiding potentially troublesome areas, including liver and gonadal tissue. We expect to file an IND for SG299 as early as 2026 and look forward to developing it in a range of B cell cancers and B-cell-mediated autoimmune diseases.
In conclusion, we're pleased with the progress to date, showing that we can overcome allogeneic and autoimmune rejection in the type 1 diabetes setting. We also have a number of programs with our allogeneic CAR-T cells, and we think this HypoImmune Platform can be broadly applicable across many cell types and diseases. We've also made progress with our Fusogen Platform in the in vivo CAR-T space and look forward to pushing this program forward. Thanks again to H.C. Wainwright, and thank you for your time.
Thank you, everyone, for joining us. We hope you enjoy the rest of your conference.