Great. Okay. Let's go ahead and get started with this session, Developing Biological Systems as Therapeutics. My name is Keay Nakae. I'm the Director of Research and one of the Senior Biotech Analysts at Chardan. Joining me for this discussion is Rich Kincaid, CFO of Healios, and Sam Reich, CEO of SAB BIO. I think the common theme here is that both companies are developing very complex biologic therapies, but in a scalable manner. Rich is focused on cell therapies. Sam is an antibody, but polyclonal antibody with a very unique manufacturing setup, but both designed to be scalable and economic. Rich, maybe let me start with you. As a cell therapy, maybe describe the basic differences between your multipotent adult progenitor cells and pluripotent stem cells that people are maybe a little more familiar with.
Well, our MAPCs don't differentiate anything. It's an end state cell. It's the basic difference. We're putting it into the body in an IV and countering acute inflammation. The cells don't survive for that long. It's two to three days, but their impact goes beyond that in terms of dampening down that inflammation and also the reparative impact that they have thereafter.
In your initial indication for ARDS, tell me what the role they play in terms of that inflammation.
Well, it's like the homeostasis drug. In the context of ARDS, there's this acute inflammatory cascade. It's happening in the lungs. Our cells, when we infuse them, we infuse them in an IV. This is an allogeneic cell therapy. It's frozen off the shelf. We thaw it, infuse it in an IV. It's very drug-like. It takes 30- 60 minutes to get it into the patient. On the first pass, it just physically goes to the lungs. It's there at the site of the acute inflammation. It's going to work through multiple inflammatory cytokines, T cells, neutrophils, macrophages, and it's going to convert those from a pro-inflammatory type to an anti-inflammatory one or to a neutral environment and restore homeostasis. In ARDS, these patients are mechanically ventilated. They're effectively drowning on their own fluid in response to this inflammatory cascade.
We showed in our phase II studies that we can get patients off a ventilator much faster. We can reduce mortality, and we do that by means of converting that inflammatory environment to one that's more one of homeostasis. We see the alveolar edema subside. The patients can breathe on their own again. We get the ventilator out faster, we reduce their risk of mortality, improve their quality of life.
Okay, you mentioned, we're talking about an allogeneic therapy as opposed to autologous. So almost by definition, that means that as a more off-the-shelf product, perhaps there are huge manufacturing scalability advantages. Specifically for you folks, when you acquired the assets from Athersys, they were actually quite far down the road in terms of effecting these manufacturing advantages. Maybe talk about what you got and where you're currently at in terms of your manufacturing.
Sure. Thanks very much, Keay. Yeah, Athersys was rather visionary in the development of the therapeutic platform, and in particular with respect to manufacturing. For those of you who follow cell therapy, you will know that manufacturing is an extraordinary challenge to make a living medicine at scale with a reasonable cost of goods, the same way extremely high-quality control, make it the same every time, all the time is not straightforward. Athersys leaned in, and they spent an extraordinary amount of money, time and effort at developing large-scale bioreactor-based manufacturing for allogeneic stem cells. We inherited that. I think, knock on wood, but it's thanks to their largesse in effect, their vision, and being early at spending a lot of money on this stuff, combined with some grant money we now have from the Japanese government.
We have sort of hundreds of millions of dollars of value that we're able to lean on for large scale, commercially viable cost of goods cell product. This was made in 3D bioreactors several years ago as they transitioned from 2D to 3D at Lonza in Singapore. That's the process we're commercializing with in Japan, and so we are going to be getting an approval in Japan in ARDS. It's a conditional approval. We've transitioned that manufacturing processes using a Sartorius 50 L bioreactor, for those of you who follow the space, but with our proprietary process, and we have that now up in a suite at Minaris in Yokohama. That's a process that Athersys developed. We've taken ownership of it. They also built up to 500 L bioreactors, same Sartorius platform, just much larger scale.
Process is a bit different, but we are now putting in place a commercial manufacturing facility in Kobe, Japan. I like to joke with people who are Japanophiles, like there is Kobe beef, and now there will be Kobe stem cells here soon, where we are funded by the Japanese government to create this large-scale 500 L bioreactor commercial facility in Kobe. Cost of goods at 50 L bioreactor stage is commercially viable, right? We can make, call it 1,000 doses a year in that suite that we have up at Minaris. We can scale it out if we need to. This is for Japan commercialization. It is plenty in the near term. We have not disclosed the COGS, but it is reasonable, and we can make a margin on it.
In cell therapy, it is a question that you all need to ask cell therapy peers of ours is, what is the commercial profile of the product? We happen to be in a really good position because of that. The 500 L process, that facility is being set up to make 40,000 doses a year. One suite makes 5,000 doses a year. Cost of goods drops by two-thirds or more when we go from 50 - 500. That is all really, again, thanks to Athersys, and they spent hundreds of millions of dollars, $653 million on the platform. We acquired that through a bankruptcy process for $2.25 million, a DIP loan we made back in early 2024. So we are counting our blessings that we are in that position. I think efficacy matters a ton, obviously, and we showed a strong indication of that in these phase IIs.
In cell therapy, in particular, manufacturing is really mission-critical.
As you mentioned, you are on a path to getting the equivalent of an accelerated approval in Japan for ARDS, but maybe talk about the advantages of being a Japanese-based company within a company that views itself as the leader in regenerative medicines, and maybe highlight some of those advantages and why that leads you to be so well-positioned to get this accelerated approval for ARDS.
That's a great question. I think Japan is leading the world in cell therapy development today in terms of the number of products that are being approved and commercialized. We started off as an iPS cell company, hence your question about pluripotent stem cells versus these MAPCs that we're developing. We were an early leader in the space. This is before Dr. Yamanaka won the Nobel Prize. The first iPS cell-derived product put into patients in the world was us. That was RPE cells in AMD patients back in 2013. Japan is kind of the land of iPS cells, as people here probably know well, but there are other products that have been approved there, too, right? There's a degree of regulatory support and path that helps one get an early approval in cell therapy that's established.
It's been around for a long time, and I think it's being optimized. There's funding, multiple sources of funding for both manufacturing. We got a $50 million grant for this 500 L facility. There's more funding, I think, emerging for global clinical studies in cell therapy. There's a promotional industrial policy in Japan that is highly cell therapy favorable, that is probably differentiated versus the U.S. I think the things that we think about in terms of our business advantages and path, and how do we optimize, Japan has a lot of cell therapy talent, a lot of strong engineers, scientists on the manufacturing side. We're doing it there first because we're commercializing there first. We're able to do it more cheaply. Though again, super weak. There's been multiple decades of very little inflation there.
Just to give you one example, one of the reasons why we moved our manufacturing from Lonza in Singapore to Minaris in Yokohama, it's a third of the cost to manufacture there. Lonza's expensive, but Lonza's great. They did a good job, but they couldn't do it at the cost that we can do in Japan just because of the labor cost is very different there. Technical acumen, very high. You see our burn, it's far less than what it would be if we had the equivalent business in the United States. It's all those things, regulatory path, funding from the government, industrial policy, cost of doing things at an early stage. But we're under no illusions. The market we need to ultimately focus on is the United States, and that's why we're running a global phase III study.
Okay. Maybe say over the next 12-24 months, what are the key milestones that investors should look for the company to achieve?
Sure. Right now, there's lots of Healios, but the focus is on ARDS, right? It's on getting an ARDS approval, and we have to get a filing done to get an approval. While we have the path cleared, for those who do cell therapy or know cell therapy, getting to a certain place with commercial manufacturing is critical to be able to file and get your approval. We've been in that for months. We did move sites from Singapore to Yokohama to Minaris, and we've got the process up. We're in the midst of some runs now to create the data that's going to take us into that filing. In the coming months, you'll see us file. After we file, nine months to approval. It's an orphan drug in Japan.
There are 28,000 patients a year in Japan, and less than 50,000 is orphan. You'll see us launch the drug. That's the Japan commercialization path. You'll hear from us on manufacturing readiness, right? You have to do process characterization along the way. Another thing we inherited from Athersys was very strong analytics, and so the characterization of the cells, the potency assays, that we have two potency assays. We're in the advanced class, and we're just getting it ready for commercial. While that's happening, you're going to see us. We initiated this study. We've initiated in Japan. We're going to open up other geographies, other sites. Ultimately, our phase III study is going to be about 80 sites globally. This is in pneumonia-induced ARDS. It's going to be heavily enrolling in the United States.
We'll have sites in the U.S., we'll have sites in Europe, we'll have sites in Korea, Taiwan, Australia. I was in Shanghai recently. We may open up a few sites in China. There's a set of milestones around that study as we make progress in it. There are other things that are going on in our business, but it's really all hands on deck on those two things, move the ball forward on to filing, to approval, to launch, successful launch, and move the study forward.
All right, well, great. Sam, let's switch to SAB. Again, let's start with your manufacturing because it is so unique. You have a herd of genetically engineered cows that are able to produce fully humanized polyclonal antibodies. Talk about how that's all set up, and then we'll talk about your lead indication in Type 1 diabetes.
Okay. Well, let's start with the class of compounds because it's not the most commonly discussed class of compounds. There's IVIG, represents about 40 commercial products with U.S. approvals and over $20 billion in revenue, and it comes into two categories, fully human IVIG, which comes from human plasma donors. Some of the companies that develop those drugs and sell those drugs are CSL, Grifols, Takeda, ADMA has come along, and they all require human donors, and the drug application or therapeutic areas are limited to what you can get from human donors. Then there are about 12 IVIG-based drugs that come from animals, and animals are used because you can vaccinate the animal and have their IgG population be targeted and have a specific therapeutic area. The notable one there is Thymoglobulin, which is a Sanofi product and is the standard of care for organ transplant.
The issue with animal IVIGs is they can only be given once. They make the patient sick, and it's kind of a one and done, and that serum sickness or that adverse event has to be outweighed by the benefit of the drug. So often those are catastrophic sort of situations. Our platform allows us to make human IVIG that's targeted, and that is a genetically engineered cow that is our animal, and that cow makes human IVIG. So we can vaccinate the cow, in the case of anti-thymocyte globulin with human thymus, purify the IVIG from the plasma of those cows, and now we have a fully human IVIG. The platform itself is a transchromosomic cow that we own that does not make bovine IVIG or IgG. It makes human IVIG.
Okay, so your initial indication, again, Type 1 diabetes. Here, I think what's great about this particular program is there's a version of ATG, the rabbit, that actually has shown quite good results. So maybe let's start there. Let's talk about what has been proven with rabbit ATG and then how your fully humanized ATG simply improves upon that.
Sure. So in Type 1 diabetes, as a first-line therapy, we want to preserve the organ. It's an autoimmune disease. The beta cells in the pancreas, which are being attacked by autoantibodies in the Type 1 diabetic patient, and the patient is losing their ability to make insulin, their own insulin, to the point at which they need exogenous insulin, which is classically known as clinical Type 1 diabetes, are now called stage three. Various companies and certainly academia and the patient advocacy groups have been looking at immunomodulation in Type 1 diabetes for decades. The most promising compound with the best data is a rabbit anti-thymocyte immunoglobulin, which is Thymoglobulin from Sanofi.
It has proven itself efficacious in multiple studies, and the endpoints which demonstrate that are preservation of C-peptide, which is the body's own endogenous insulin production, as well as reduction in HbA1c, which is showing that those patients with their own insulin have better glycemic control than a patient on placebo. That has been shown with Thymoglobulin in two separate statistically significant randomized double-blinded trials. One is called TN19, one is called MELD-ATG, which was recently published in Lancet. There is a tremendous amount of efficacy, enough to get the drug approved, demonstrated by this rabbit anti-thymocyte immunoglobulin. But because it is rabbit, it is foreign IVIG, it cannot be redosed. This is a chronic disease which requires redosing, and it also has adverse effects which may not be acceptable in T1D.
Where they are perfectly acceptable in organ transplant, in T1D, Sanofi at least has made the decision not to commercialize anti-thymocyte globulin, and in fact, to go with a different product, which is called Tzield. This is where our cow can solve a problem, and we have a highly de-risked approach because we can make the human version of a drug we know is efficacious. We have already demonstrated that as a human IVIG, it can be redosed, and it does not cause serum sickness, so it has a more palatable and acceptable safety profile. This is where our cow allows us to solve a problem, which is that animal IVIGs are not safe enough or redosable for certain applications. We know rabbit anti-thymocyte globulin works. It is non-controversial, firmly established, and demonstrated by the data, but it is not safe enough, and it cannot be redosed.
We make an anti-thymocyte globulin in our cow, which we have demonstrated has that same activity, which is proven to be efficacious, and we can redose, and we can give it safely.
Okay. Maybe you have phase I data, and maybe just talk about what you were able to see in the cohort of diabetic patients and then the ability to redose in the healthy volunteers.
Yes. We did a pretty substantial phase I, which I think had over 80 subjects and patients overall. We dose escalated, and most of the patients were adult healthy subjects, so they did not have Type 1 diabetes. In those adult healthies, we showed that the drug didn't cause serum sickness. We demonstrated that the drug could be redosed safely. Then we added a patient cohort. We looked at a small group of patients with Type 1 diabetes, and the patients that got our drug had preserved C-peptide. In fact, on average, had absolute increase in C-peptide. In a small group of patients, in an open label fashion, we did show proof of concept, which is that the patients that got our drug had preserved C-peptide, which is the primary endpoint.
That all went to complement the fact that in all the adult healthies, we showed that our drug has the same mechanism of action as Thymoglobulin, which has been proven to be efficacious.
Okay, so you're now enrolling in potentially registrational phase II SAFEGUARD, and maybe quickly just outline the study design and the primary endpoints.
The SAFEGUARD study, which has been enrolling this year and is near completion of enrollment, is a pivotal study. It's called a phase II-B, but it has registrational endpoints. We have agreement with FDA that it is a registrational study. It is 159 patients broken into three cohorts, a higher dose, a lower dose, and a placebo, 1:1:1 . These patients are newly diagnosed with Type 1 diabetes, ages five to 40. The primary endpoint is C-peptide, where we intend to show preservation of C-peptide versus placebo, and that shows that the drug is working. We're preserving the organ, we're preserving the patient's ability to make insulin. That is the accepted primary endpoint.
The key secondary endpoint is HbA1c, which is a clinical endpoint, which we hope to show that we will reduce HbA1c in the treated groups, and therefore that patient that has preserved C-peptide, they are making their own insulin, also has improved glycemic control. That package of patients and endpoints are powered and the data, we have agreement with FDA, is sufficient for approval.
Okay. You mentioned Tzield earlier. Again, it is not an ATG. It works differently, but it has similarities in terms of trying to achieve T-cell exhaustion. Importantly, more recently, the FDA granted an expanded indication for Tzield based on C-peptide. Maybe highlight for the audience the importance of that regulatory acknowledgment of the validity of C-peptide.
Yeah. A huge question in diabetes and getting new drugs approved for diabetes has been what is required for approval? Tzield was approved in June, so now we know what is required for approval. It was approved on C-peptide alone because in their phase III, Tzield did not demonstrate any other benefit. It missed all the other secondary endpoints. The C-peptide is a biologic marker. It is not a clinical presentation. There was a lot of question whether that would be sufficient for an approval, and it basically was understood not to be sufficient. Then Tzield got approved, having only shown C-peptide. It is an accelerated approval. They still need to demonstrate clinical benefit, but post-marketing. The drug is now commercial. That resolved the big question, which is what is required for approval.
We now know from precedent, from the Tzield approval, that C-peptide is sufficient for an accelerated approval. With that said, Thymoglobulin has always demonstrated reduction in HbA1c and with C-peptide and any clinical endpoint, HbA1c being the most discussed one, that is a full approval.
Okay, and then finally, you have started another phase III PRISE, and that is led by Dr. Haller, who was again, one of the PIs in the rabbit studies. Talk about the key benefits that having data from that study will provide you.
Yes. In immunomodulation in Type 1 diabetes or using drugs to preserve the patient's ability to make their own insulin, as measured by C-peptide, the clinical development and clinical strategy has always focused on patients that are newly diagnosed within some time frame from diagnosis. Tzield, which is approved, is within the first 8 weeks of diagnosis. For clinical strategy and minimizing risk, we always want to have the most homogeneous population possible, which ends up excluding certain patients from being studied in clinical research and then from being indicated on the label of the drug. The PRISE study aims to get more patients on drugs, study more patients. Our SAFEGUARD study, which will be our initial label, is limited to patients within 100 days of diagnosis. What Dr. Haller and Breakthrough T1D wanted to study is patients beyond 100 days.
The PRISE study has the first 100-day cohort as the control group, and then a cohort of patients up to one year, and a third cohort three, from patients one year to two years of diagnosis. What this does is it aims to demonstrate that what is important is C-peptide or the patient's ability to make insulin and not the time from diagnosis. If that study is successful, that will also read onto the label and patients up to two years from diagnosis will be eligible for therapy, which increases the total addressable market as well as the ability to penetrate that market.
Okay. Well, great. We have reached the end of our time here, but hopefully you can appreciate that in the case of Rich, a potential approval in 2027, in the case of Sam, some very important clinical data in 2027. Thank you.
Thank you.
Thank you.